CHEST 2013

CHICAGO – Targeted biological therapies are working in rheumatoid arthritis, cancer, and irritable bowel disease, leading some experts to question whether their time in asthma has finally arrived.

"We’re still not there yet, but perhaps we can see the light at the end of the tunnel," Dr. Diego J. Maselli said at the annual meeting of the American College of Chest Physicians.

Early successes in animal models of asthma have not translated to humans with asthma, in part because of disparities in immunology, biology, and anatomy, but also because of the heterogeneous nature of the disease.

The benchmark so far for asthma biologics is the anti-immunoglobulin E (anti-IgE) monoclonal antibody omalizumab (Xolair), indicated for moderate to severe persistent asthma that is uncontrolled with inhaled corticosteroids.

Omalizumab gained approval after cutting exacerbations in two trials involving patients with a forced expiratory volume in one second (FEV₁) between 40% and 80% predicted, but the drug had no effect on exacerbations in a third trial that did not restrict screening FEV₁ and allowed use of long-acting beta₂-agonists. In all three studies, exacerbations were not reduced in patients requiring oral steroids as maintenance therapy or those with an FEV₁ over 80%.

There is now significant experience with omalizumab, and although there was a concern regarding a slight increase in the incidence of malignancy in the initial studies, large registries have shown no risk for malignant neoplasms or cardiovascular effects, said Dr. Maselli, of the University of Texas Health Science Center, San Antonio.

Promising results with several new agents, however, suggest that phenotypical markers such as IgE, eosinophils, and periostin are necessary to identify patients most likely to benefit from targeted therapy, he noted.

For example, the investigational interleukin 5 (IL-5) antagonist mepolizumab produced mixed initial results, but reduced asthma exacerbations over the course of 50 weeks from a mean of 3.4 to 2 in one study (N. Engl. J. Med. 2009;360:973-84), and by 48% over placebo in a second study when used in highly selected asthma patient populations with confirmed sputum or serum eosinophilia (Lancet 2012;380:651-9).

A recent meta-analysis (PLOS One 2013 March 27 [10.1371/journal.pone.0059872]) of seven mepolizumab studies echoed these findings, but also concluded the drug fails to significantly improve lung function, Dr. Maselli observed.

Provocative results from another biologic suggest that the presence of nasal polyps in eosinophilic asthma may be useful in further selecting patients for IL-5 antagonist therapy. Intravenous treatment with the anti-IL-5 antibody reslizumab (Cinquil) had a greater effect on sputum eosinophilia and asthma exacerbations in poorly controlled asthmatics with nasal polyps (Am. J. Respir. Crit. Care. Med. 2011;184:1125-32).

Serum levels of the matricellular protein periostin are also being used to better target interleukin-13 (IL-13)-directed therapy, Dr. Maselli said. IL-13 induces bronchial epithelial cells to secrete periostin and is thought to play a central role in asthma by promoting mucus secretion and airway remodeling and hyper-reactivity.

Six monthly injections of the experimental anti-IL-13 monoclonal antibody lebrikizumab significantly improved lung function over placebo in asthmatics poorly controlled on inhaled corticosteroids, but produced a more robust increase in FEV₁ and a 60% reduction in exacerbations only in the subgroup with high pretreatment periostin levels (N. Engl. J. Med. 2011;365:1088-98). Interestingly, the investigators had hypothesized that high serum IgE plus high peripheral-blood eosinophil counts would serve as a marker for patients with high IL-13 expression.

To further complicate IL-13 blockade, a more recent lebrikizumab study in asthmatic patients not receiving inhaled steroids reported no meaningful differences in FEV₁ between various lebrikizumab dose groups and placebo in a periostin subgroup (J. Allergy Clin. Immunol. 2013;132:567-574.e12).

The investigational anti-IL-13 monoclonal antibody tralokinumab also recently failed to meet its primary endpoint of improving Asthma Control Questionnaire scores compared with placebo and modestly improved FEV₁ in a phase II study (Eur. Respir. J. 2013;41:330-8).

Finally, strong phase II results are being seen with dupilumab, a monoclonal antibody that inhibits both IL-4 and IL-13 signaling, Dr. Maselli said. Dupilumab cut exacerbations by a dramatic 87%, improved lung function, and decreased biomarkers associated with type 2 helper T-cell-driven inflammation in patients with elevated eosinophil levels and moderate to severe uncontrolled asthma despite use of glucocorticosteroids and long-acting beta-agonists (N. Engl. J. Med. 2013;368:2455-66).

"These agents allow clinicians to target specific asthma phenotypes with the aid of biomarkers such as IgE, eosinophilia, and periostin, and show a glimpse of what the future of ‘personalized medicine’ may offer," he said in an interview. "Ongoing studies will help elucidate which of these newer therapies will prove effective and safe for these difficult-to-treat asthmatics."

Dr. Maselli reported having no financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Targeted biological therapies are working in rheumatoid arthritis, cancer, and irritable bowel disease, leading some experts to question whether their time in asthma has finally arrived.

"We’re still not there yet, but perhaps we can see the light at the end of the tunnel," Dr. Diego J. Maselli said at the annual meeting of the American College of Chest Physicians.

Early successes in animal models of asthma have not translated to humans with asthma, in part because of disparities in immunology, biology, and anatomy, but also because of the heterogeneous nature of the disease.

The benchmark so far for asthma biologics is the anti-immunoglobulin E (anti-IgE) monoclonal antibody omalizumab (Xolair), indicated for moderate to severe persistent asthma that is uncontrolled with inhaled corticosteroids.

Omalizumab gained approval after cutting exacerbations in two trials involving patients with a forced expiratory volume in one second (FEV₁) between 40% and 80% predicted, but the drug had no effect on exacerbations in a third trial that did not restrict screening FEV₁ and allowed use of long-acting beta₂-agonists. In all three studies, exacerbations were not reduced in patients requiring oral steroids as maintenance therapy or those with an FEV₁ over 80%.

There is now significant experience with omalizumab, and although there was a concern regarding a slight increase in the incidence of malignancy in the initial studies, large registries have shown no risk for malignant neoplasms or cardiovascular effects, said Dr. Maselli, of the University of Texas Health Science Center, San Antonio.

Promising results with several new agents, however, suggest that phenotypical markers such as IgE, eosinophils, and periostin are necessary to identify patients most likely to benefit from targeted therapy, he noted.

For example, the investigational interleukin 5 (IL-5) antagonist mepolizumab produced mixed initial results, but reduced asthma exacerbations over the course of 50 weeks from a mean of 3.4 to 2 in one study (N. Engl. J. Med. 2009;360:973-84), and by 48% over placebo in a second study when used in highly selected asthma patient populations with confirmed sputum or serum eosinophilia (Lancet 2012;380:651-9).

A recent meta-analysis (PLOS One 2013 March 27 [10.1371/journal.pone.0059872]) of seven mepolizumab studies echoed these findings, but also concluded the drug fails to significantly improve lung function, Dr. Maselli observed.

Provocative results from another biologic suggest that the presence of nasal polyps in eosinophilic asthma may be useful in further selecting patients for IL-5 antagonist therapy. Intravenous treatment with the anti-IL-5 antibody reslizumab (Cinquil) had a greater effect on sputum eosinophilia and asthma exacerbations in poorly controlled asthmatics with nasal polyps (Am. J. Respir. Crit. Care. Med. 2011;184:1125-32).

Serum levels of the matricellular protein periostin are also being used to better target interleukin-13 (IL-13)-directed therapy, Dr. Maselli said. IL-13 induces bronchial epithelial cells to secrete periostin and is thought to play a central role in asthma by promoting mucus secretion and airway remodeling and hyper-reactivity.

Six monthly injections of the experimental anti-IL-13 monoclonal antibody lebrikizumab significantly improved lung function over placebo in asthmatics poorly controlled on inhaled corticosteroids, but produced a more robust increase in FEV₁ and a 60% reduction in exacerbations only in the subgroup with high pretreatment periostin levels (N. Engl. J. Med. 2011;365:1088-98). Interestingly, the investigators had hypothesized that high serum IgE plus high peripheral-blood eosinophil counts would serve as a marker for patients with high IL-13 expression.

To further complicate IL-13 blockade, a more recent lebrikizumab study in asthmatic patients not receiving inhaled steroids reported no meaningful differences in FEV₁ between various lebrikizumab dose groups and placebo in a periostin subgroup (J. Allergy Clin. Immunol. 2013;132:567-574.e12).

The investigational anti-IL-13 monoclonal antibody tralokinumab also recently failed to meet its primary endpoint of improving Asthma Control Questionnaire scores compared with placebo and modestly improved FEV₁ in a phase II study (Eur. Respir. J. 2013;41:330-8).

Finally, strong phase II results are being seen with dupilumab, a monoclonal antibody that inhibits both IL-4 and IL-13 signaling, Dr. Maselli said. Dupilumab cut exacerbations by a dramatic 87%, improved lung function, and decreased biomarkers associated with type 2 helper T-cell-driven inflammation in patients with elevated eosinophil levels and moderate to severe uncontrolled asthma despite use of glucocorticosteroids and long-acting beta-agonists (N. Engl. J. Med. 2013;368:2455-66).

"These agents allow clinicians to target specific asthma phenotypes with the aid of biomarkers such as IgE, eosinophilia, and periostin, and show a glimpse of what the future of ‘personalized medicine’ may offer," he said in an interview. "Ongoing studies will help elucidate which of these newer therapies will prove effective and safe for these difficult-to-treat asthmatics."

Dr. Maselli reported having no financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Targeted biological therapies are working in rheumatoid arthritis, cancer, and irritable bowel disease, leading some experts to question whether their time in asthma has finally arrived.

"We’re still not there yet, but perhaps we can see the light at the end of the tunnel," Dr. Diego J. Maselli said at the annual meeting of the American College of Chest Physicians.

Early successes in animal models of asthma have not translated to humans with asthma, in part because of disparities in immunology, biology, and anatomy, but also because of the heterogeneous nature of the disease.

The benchmark so far for asthma biologics is the anti-immunoglobulin E (anti-IgE) monoclonal antibody omalizumab (Xolair), indicated for moderate to severe persistent asthma that is uncontrolled with inhaled corticosteroids.

Omalizumab gained approval after cutting exacerbations in two trials involving patients with a forced expiratory volume in one second (FEV₁) between 40% and 80% predicted, but the drug had no effect on exacerbations in a third trial that did not restrict screening FEV₁ and allowed use of long-acting beta₂-agonists. In all three studies, exacerbations were not reduced in patients requiring oral steroids as maintenance therapy or those with an FEV₁ over 80%.

There is now significant experience with omalizumab, and although there was a concern regarding a slight increase in the incidence of malignancy in the initial studies, large registries have shown no risk for malignant neoplasms or cardiovascular effects, said Dr. Maselli, of the University of Texas Health Science Center, San Antonio.

Promising results with several new agents, however, suggest that phenotypical markers such as IgE, eosinophils, and periostin are necessary to identify patients most likely to benefit from targeted therapy, he noted.

For example, the investigational interleukin 5 (IL-5) antagonist mepolizumab produced mixed initial results, but reduced asthma exacerbations over the course of 50 weeks from a mean of 3.4 to 2 in one study (N. Engl. J. Med. 2009;360:973-84), and by 48% over placebo in a second study when used in highly selected asthma patient populations with confirmed sputum or serum eosinophilia (Lancet 2012;380:651-9).

A recent meta-analysis (PLOS One 2013 March 27 [10.1371/journal.pone.0059872]) of seven mepolizumab studies echoed these findings, but also concluded the drug fails to significantly improve lung function, Dr. Maselli observed.

Provocative results from another biologic suggest that the presence of nasal polyps in eosinophilic asthma may be useful in further selecting patients for IL-5 antagonist therapy. Intravenous treatment with the anti-IL-5 antibody reslizumab (Cinquil) had a greater effect on sputum eosinophilia and asthma exacerbations in poorly controlled asthmatics with nasal polyps (Am. J. Respir. Crit. Care. Med. 2011;184:1125-32).

Serum levels of the matricellular protein periostin are also being used to better target interleukin-13 (IL-13)-directed therapy, Dr. Maselli said. IL-13 induces bronchial epithelial cells to secrete periostin and is thought to play a central role in asthma by promoting mucus secretion and airway remodeling and hyper-reactivity.

Six monthly injections of the experimental anti-IL-13 monoclonal antibody lebrikizumab significantly improved lung function over placebo in asthmatics poorly controlled on inhaled corticosteroids, but produced a more robust increase in FEV₁ and a 60% reduction in exacerbations only in the subgroup with high pretreatment periostin levels (N. Engl. J. Med. 2011;365:1088-98). Interestingly, the investigators had hypothesized that high serum IgE plus high peripheral-blood eosinophil counts would serve as a marker for patients with high IL-13 expression.

To further complicate IL-13 blockade, a more recent lebrikizumab study in asthmatic patients not receiving inhaled steroids reported no meaningful differences in FEV₁ between various lebrikizumab dose groups and placebo in a periostin subgroup (J. Allergy Clin. Immunol. 2013;132:567-574.e12).

The investigational anti-IL-13 monoclonal antibody tralokinumab also recently failed to meet its primary endpoint of improving Asthma Control Questionnaire scores compared with placebo and modestly improved FEV₁ in a phase II study (Eur. Respir. J. 2013;41:330-8).

Finally, strong phase II results are being seen with dupilumab, a monoclonal antibody that inhibits both IL-4 and IL-13 signaling, Dr. Maselli said. Dupilumab cut exacerbations by a dramatic 87%, improved lung function, and decreased biomarkers associated with type 2 helper T-cell-driven inflammation in patients with elevated eosinophil levels and moderate to severe uncontrolled asthma despite use of glucocorticosteroids and long-acting beta-agonists (N. Engl. J. Med. 2013;368:2455-66).

"These agents allow clinicians to target specific asthma phenotypes with the aid of biomarkers such as IgE, eosinophilia, and periostin, and show a glimpse of what the future of ‘personalized medicine’ may offer," he said in an interview. "Ongoing studies will help elucidate which of these newer therapies will prove effective and safe for these difficult-to-treat asthmatics."

Dr. Maselli reported having no financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Accurate phenotyping, in the ascendant over the last decade, equates with more effectively targeted treatments for chronic obstructive pulmonary disease, according to a proponent of personalized pulmonary medicine.

"We know that COPD is not the same, but right now we are treating these patients as though one size fits all," Dr. Nicola A. Hanania of the Baylor College of Medicine, Houston, said in a packed session on COPD at the annual meeting of the American College of Chest Physicians.

Because phenotypes describe differences in individuals, they should have relevance to clinically meaningful outcomes. "In COPD, that relates to symptoms, exacerbation, disease progression, response to therapy, and survival," he said.

Potential phenotypes that have been identified according to clinical, physiologic, and radiologic criteria include chronic bronchitis, asthma/COPD overlap, frequent exacerbator, radiologic CT, and persistent systemic inflammation.

Chronic bronchitis

Chronic bronchitis tends to occur more in younger people who smoke. It also is characterized by more wheezing and thicker airway walls. Data presented by Dr. Hanania also showed that this phenotype has more frequent acute exacerbations (Chest 2011;140:1107-8).

In one study, 290 subjects deemed chronically bronchitic – chronic cough and phlegm lasting 3 months of every year for 2 consecutive years – were compared with 771 subjects who were not chronically bronchitic. Investigators found that patients in the first group had more frequent exacerbations per patient: 1.21-1.62 vs. 0.63-1.12 (P < .027). The first group also reported more severe exacerbations: 26.6% vs. 20% (P < .024) (Chest 2011;140:626-33).

Asthma/COPD overlap

"This is a phenotype that deserves more attention. We all have patients where we scratch our head, ‘Is this asthma, or is this COPD?’ " said Dr. Hanania. "We don’t really know because these patients are notoriously excluded from both asthma and COPD studies." He cited estimates suggesting that 13%-20% of COPD patients overlap with asthma (Arch. Bronconeumol. 2012;48:331-7).

Proposed diagnostic criteria for the overlap syndrome phenotype may include two major criteria: marked response to bronchodilators (>15% and >400 mL in forced expiratory volume in 1 second [FEV₁]), history of asthma if patient is younger than 40 years, and sputum eosinophilia. Overlap also can be diagnosed by one major criterion and two of the following: response to bronchodilation at least two separate times (>12% and >200 mL in FEV₁), history of atopy, and increased total serum IgE. At this time, he said, these criteria are based on expert opinion and on data, "but the clinical implications, once we do the homework, is that these patients deserve to be on antibiotics and corticosteroids early on."

Frequent exacerbator

Defined in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines as two or more exacerbations per year, the frequent exacerbator phenotype was explained in the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), Dr. Hanania said, which showed that, although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype (N. Engl. J. Med. 2010; 363:1128-38).

Frequent exacerbators have higher-stage COPD, more severe obstruction, and more hospitalizations, Dr. Hanania noted.

In addition, the ECLIPSE investigators found that, in 2,138 patients, frequent exacerbator types had an odds ratio of 5.72 of having had an exacerbation in the previous year

Although there other risk factors implicating this phenotype, "the most important question to ask the patient is whether they have had an exacerbation in the previous year," he said. Chronic cough is another factor.

The clinical benefit to identifying the frequent exacerbator, according to Dr. Hanania, is that this group has a greater range of comorbidities, including more inflammation, heightened viral susceptibility, and increased cardiovascular risk, among other susceptibilities.

Using CT for phenotyping

Noting that radiologic phenotyping in COPD is more advanced than in asthma at this time, Dr. Hanania said that quantitative and visual assessment of CT radiographs is "promising" and has helped identify COPD subphenotypes such as emphysema because of accurate assessment of lung inflation, wall thickness, and other factors.

Identifying patients with bronchiectasis, pulmonary arterial enlargement, and acute exacerbations in COPD is also possible with CT radiography, making it possible to predict the different outcomes in each situation. "The clinical implication is that these patients tend to have more frequent exacerbation, worse lung function, and infection," he said, noting that nascent research using imaging to determine biomarkers in functional small airways disease also is occurring.

Systemic inflammation

In the ECLIPSE study, 2,164 COPD patients had an odds ratio of 2.23 for being a current smoker and had higher levels of inflammation, as determined using biomarkers such as C-reactive protein, compared with 337 smokers without COPD and 245 nonsmokers. At the 3-year follow-up, this group with persistently higher inflammation also was classified as having significantly higher all-cause mortality than the group with less inflammation (13% vs. 2%); exacerbation rates in this group were also persistently higher (1.5 vs. 0.9) (PLoS ONE 2012;7:e37483).

Therapeutic implications

Coupling these phenotypes with molecular descriptions of mechanisms and their underlying pathologies can lead to accurate, personalized treatment of COPD. "Phenotypes without clear implications for prognosis and treatment are of little clinical use," Dr. Hanania said, noting that longitudinal studies to validate these phenotypes are necessary.

"Research can help identify mechanisms and courses in different phenotypes, including gender differences," he concluded. "Examining therapeutic responses to different phenotypes can lead to future interventions."

Dr. Hanania disclosed several relationships with a variety of pharmaceutical and medical manufacturers, including Genentech, GlaxoSmithKline* and Astra Zeneca.

Beyond GOLD: A tale of two COPD guidelines

Both address severity and comorbidity, but only one COPD guideline takes into account the latest research on phenotyping in chronic obstructive pulmonary disease.

"The GOLD guidelines do not include clinical phenotypes," said Dr. Joan Soriano, a presenter at the meeting. "But the Spanish ones do."

In fact, there is really only one area where the two documents overlap, said Dr. Soriano: how they define COPD, and even that is not the same. "They both mention the fundamental aspect, which is airflow limitation, and also that the mechanism involved is inflammation," he said. The GOLD definition, however, recognizes the importance of comorbidities, which the Spanish guidelines address the role of tobacco and symptomology.

GOLD (Global Initiative for Chronic Obstructive Lung Disease) is an organization of health care professionals from around the world. "I am not a member of GOLD," Dr. Soriano told the packed session.

The Spanish guidelines are issued by SEPAR, the Spanish Society for Pneumology and Thoracic Surgery. Dr. Soriano is the director of epidemiology and clinical research at the International Center of Advanced Respiratory Medicine (CIMERA) in Palma, Spain.

How the two approach diagnosis also differs. The Spanish guidelines begin with the general COPD diagnosis, then move to the characterization and phenotype, then move to the severity of the disease. They are more specific about age (over 35 years), and have lower limit of normal (LLN) values for persons aged over 70 years and less than 50 years. The GOLD guidelines do not address LLN.

To characterize the disease specifically, the Spanish guidelines address the existence of phenotypes, according to Dr. Soriano, beginning with determining the frequency of exacerbation the patient has per year, and then classifying them eventually into four types: mixed, chronic bronchitis, emphysema, and exacerbator. The GOLD guidelines do not mention phenotypes.

When it comes to the multidimensional assessment of COPD, "the GOLD guidelines lump the mild with the severe spirometry. This is very hard for me to understand," he said. Other classification divergence includes that the Spanish guidelines consider the BODE index.

Treatment in the two guidelines begins similarly, but vectors off from there. "Basically, we are looking at the same trials, so the initial treatments should be short-acting bronchodilators," Dr. Soriano said, but because phenotyping allows for more targeted treatment, the Spanish guidelines offer more detailed treatment options.

In a paper coauthored by Dr. Soriano earlier this year, specific treatment per phenotype included phosphodiesterase-4 inhibitors only for those with chronic bronchitis, inhaled corticosteroids for overlap COPD-asthma, and bronchodilators for infrequent exacerbators (Eur. Respir. J. 2013;41:1252-6).

In the end, the guidelines might not follow the same trajectory, but each has value, he said. "Whatever guidelines you choose, don’t go back and forth. Pick one and use them."

Dr. Soriano reported relationships with Novartis Spain, AstraZeneca, Pfizer, and several other pharmaceutical and medical manufacturers.

wmcknight@frontlinemedcom.com

*CORRECTION, 2/20/2014: An earlier version of this story misstated the name of GlaxoSmithKline.

CHICAGO – Accurate phenotyping, in the ascendant over the last decade, equates with more effectively targeted treatments for chronic obstructive pulmonary disease, according to a proponent of personalized pulmonary medicine.

"We know that COPD is not the same, but right now we are treating these patients as though one size fits all," Dr. Nicola A. Hanania of the Baylor College of Medicine, Houston, said in a packed session on COPD at the annual meeting of the American College of Chest Physicians.

Because phenotypes describe differences in individuals, they should have relevance to clinically meaningful outcomes. "In COPD, that relates to symptoms, exacerbation, disease progression, response to therapy, and survival," he said.

Potential phenotypes that have been identified according to clinical, physiologic, and radiologic criteria include chronic bronchitis, asthma/COPD overlap, frequent exacerbator, radiologic CT, and persistent systemic inflammation.

Chronic bronchitis

Chronic bronchitis tends to occur more in younger people who smoke. It also is characterized by more wheezing and thicker airway walls. Data presented by Dr. Hanania also showed that this phenotype has more frequent acute exacerbations (Chest 2011;140:1107-8).

In one study, 290 subjects deemed chronically bronchitic – chronic cough and phlegm lasting 3 months of every year for 2 consecutive years – were compared with 771 subjects who were not chronically bronchitic. Investigators found that patients in the first group had more frequent exacerbations per patient: 1.21-1.62 vs. 0.63-1.12 (P < .027). The first group also reported more severe exacerbations: 26.6% vs. 20% (P < .024) (Chest 2011;140:626-33).

Asthma/COPD overlap

"This is a phenotype that deserves more attention. We all have patients where we scratch our head, ‘Is this asthma, or is this COPD?’ " said Dr. Hanania. "We don’t really know because these patients are notoriously excluded from both asthma and COPD studies." He cited estimates suggesting that 13%-20% of COPD patients overlap with asthma (Arch. Bronconeumol. 2012;48:331-7).

Proposed diagnostic criteria for the overlap syndrome phenotype may include two major criteria: marked response to bronchodilators (>15% and >400 mL in forced expiratory volume in 1 second [FEV₁]), history of asthma if patient is younger than 40 years, and sputum eosinophilia. Overlap also can be diagnosed by one major criterion and two of the following: response to bronchodilation at least two separate times (>12% and >200 mL in FEV₁), history of atopy, and increased total serum IgE. At this time, he said, these criteria are based on expert opinion and on data, "but the clinical implications, once we do the homework, is that these patients deserve to be on antibiotics and corticosteroids early on."

Frequent exacerbator

Defined in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines as two or more exacerbations per year, the frequent exacerbator phenotype was explained in the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), Dr. Hanania said, which showed that, although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype (N. Engl. J. Med. 2010; 363:1128-38).

Frequent exacerbators have higher-stage COPD, more severe obstruction, and more hospitalizations, Dr. Hanania noted.

In addition, the ECLIPSE investigators found that, in 2,138 patients, frequent exacerbator types had an odds ratio of 5.72 of having had an exacerbation in the previous year

Although there other risk factors implicating this phenotype, "the most important question to ask the patient is whether they have had an exacerbation in the previous year," he said. Chronic cough is another factor.

The clinical benefit to identifying the frequent exacerbator, according to Dr. Hanania, is that this group has a greater range of comorbidities, including more inflammation, heightened viral susceptibility, and increased cardiovascular risk, among other susceptibilities.

Using CT for phenotyping

Noting that radiologic phenotyping in COPD is more advanced than in asthma at this time, Dr. Hanania said that quantitative and visual assessment of CT radiographs is "promising" and has helped identify COPD subphenotypes such as emphysema because of accurate assessment of lung inflation, wall thickness, and other factors.

Identifying patients with bronchiectasis, pulmonary arterial enlargement, and acute exacerbations in COPD is also possible with CT radiography, making it possible to predict the different outcomes in each situation. "The clinical implication is that these patients tend to have more frequent exacerbation, worse lung function, and infection," he said, noting that nascent research using imaging to determine biomarkers in functional small airways disease also is occurring.

Systemic inflammation

In the ECLIPSE study, 2,164 COPD patients had an odds ratio of 2.23 for being a current smoker and had higher levels of inflammation, as determined using biomarkers such as C-reactive protein, compared with 337 smokers without COPD and 245 nonsmokers. At the 3-year follow-up, this group with persistently higher inflammation also was classified as having significantly higher all-cause mortality than the group with less inflammation (13% vs. 2%); exacerbation rates in this group were also persistently higher (1.5 vs. 0.9) (PLoS ONE 2012;7:e37483).

Therapeutic implications

Coupling these phenotypes with molecular descriptions of mechanisms and their underlying pathologies can lead to accurate, personalized treatment of COPD. "Phenotypes without clear implications for prognosis and treatment are of little clinical use," Dr. Hanania said, noting that longitudinal studies to validate these phenotypes are necessary.

"Research can help identify mechanisms and courses in different phenotypes, including gender differences," he concluded. "Examining therapeutic responses to different phenotypes can lead to future interventions."

Dr. Hanania disclosed several relationships with a variety of pharmaceutical and medical manufacturers, including Genentech, GlaxoSmithKline* and Astra Zeneca.

Beyond GOLD: A tale of two COPD guidelines

Both address severity and comorbidity, but only one COPD guideline takes into account the latest research on phenotyping in chronic obstructive pulmonary disease.

"The GOLD guidelines do not include clinical phenotypes," said Dr. Joan Soriano, a presenter at the meeting. "But the Spanish ones do."

In fact, there is really only one area where the two documents overlap, said Dr. Soriano: how they define COPD, and even that is not the same. "They both mention the fundamental aspect, which is airflow limitation, and also that the mechanism involved is inflammation," he said. The GOLD definition, however, recognizes the importance of comorbidities, which the Spanish guidelines address the role of tobacco and symptomology.

GOLD (Global Initiative for Chronic Obstructive Lung Disease) is an organization of health care professionals from around the world. "I am not a member of GOLD," Dr. Soriano told the packed session.

The Spanish guidelines are issued by SEPAR, the Spanish Society for Pneumology and Thoracic Surgery. Dr. Soriano is the director of epidemiology and clinical research at the International Center of Advanced Respiratory Medicine (CIMERA) in Palma, Spain.

How the two approach diagnosis also differs. The Spanish guidelines begin with the general COPD diagnosis, then move to the characterization and phenotype, then move to the severity of the disease. They are more specific about age (over 35 years), and have lower limit of normal (LLN) values for persons aged over 70 years and less than 50 years. The GOLD guidelines do not address LLN.

To characterize the disease specifically, the Spanish guidelines address the existence of phenotypes, according to Dr. Soriano, beginning with determining the frequency of exacerbation the patient has per year, and then classifying them eventually into four types: mixed, chronic bronchitis, emphysema, and exacerbator. The GOLD guidelines do not mention phenotypes.

When it comes to the multidimensional assessment of COPD, "the GOLD guidelines lump the mild with the severe spirometry. This is very hard for me to understand," he said. Other classification divergence includes that the Spanish guidelines consider the BODE index.

Treatment in the two guidelines begins similarly, but vectors off from there. "Basically, we are looking at the same trials, so the initial treatments should be short-acting bronchodilators," Dr. Soriano said, but because phenotyping allows for more targeted treatment, the Spanish guidelines offer more detailed treatment options.

In a paper coauthored by Dr. Soriano earlier this year, specific treatment per phenotype included phosphodiesterase-4 inhibitors only for those with chronic bronchitis, inhaled corticosteroids for overlap COPD-asthma, and bronchodilators for infrequent exacerbators (Eur. Respir. J. 2013;41:1252-6).

In the end, the guidelines might not follow the same trajectory, but each has value, he said. "Whatever guidelines you choose, don’t go back and forth. Pick one and use them."

Dr. Soriano reported relationships with Novartis Spain, AstraZeneca, Pfizer, and several other pharmaceutical and medical manufacturers.

wmcknight@frontlinemedcom.com

*CORRECTION, 2/20/2014: An earlier version of this story misstated the name of GlaxoSmithKline.

CHICAGO – Accurate phenotyping, in the ascendant over the last decade, equates with more effectively targeted treatments for chronic obstructive pulmonary disease, according to a proponent of personalized pulmonary medicine.

"We know that COPD is not the same, but right now we are treating these patients as though one size fits all," Dr. Nicola A. Hanania of the Baylor College of Medicine, Houston, said in a packed session on COPD at the annual meeting of the American College of Chest Physicians.

Because phenotypes describe differences in individuals, they should have relevance to clinically meaningful outcomes. "In COPD, that relates to symptoms, exacerbation, disease progression, response to therapy, and survival," he said.

Potential phenotypes that have been identified according to clinical, physiologic, and radiologic criteria include chronic bronchitis, asthma/COPD overlap, frequent exacerbator, radiologic CT, and persistent systemic inflammation.

Chronic bronchitis

Chronic bronchitis tends to occur more in younger people who smoke. It also is characterized by more wheezing and thicker airway walls. Data presented by Dr. Hanania also showed that this phenotype has more frequent acute exacerbations (Chest 2011;140:1107-8).

In one study, 290 subjects deemed chronically bronchitic – chronic cough and phlegm lasting 3 months of every year for 2 consecutive years – were compared with 771 subjects who were not chronically bronchitic. Investigators found that patients in the first group had more frequent exacerbations per patient: 1.21-1.62 vs. 0.63-1.12 (P < .027). The first group also reported more severe exacerbations: 26.6% vs. 20% (P < .024) (Chest 2011;140:626-33).

Asthma/COPD overlap

"This is a phenotype that deserves more attention. We all have patients where we scratch our head, ‘Is this asthma, or is this COPD?’ " said Dr. Hanania. "We don’t really know because these patients are notoriously excluded from both asthma and COPD studies." He cited estimates suggesting that 13%-20% of COPD patients overlap with asthma (Arch. Bronconeumol. 2012;48:331-7).

Proposed diagnostic criteria for the overlap syndrome phenotype may include two major criteria: marked response to bronchodilators (>15% and >400 mL in forced expiratory volume in 1 second [FEV₁]), history of asthma if patient is younger than 40 years, and sputum eosinophilia. Overlap also can be diagnosed by one major criterion and two of the following: response to bronchodilation at least two separate times (>12% and >200 mL in FEV₁), history of atopy, and increased total serum IgE. At this time, he said, these criteria are based on expert opinion and on data, "but the clinical implications, once we do the homework, is that these patients deserve to be on antibiotics and corticosteroids early on."

Frequent exacerbator

Defined in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines as two or more exacerbations per year, the frequent exacerbator phenotype was explained in the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), Dr. Hanania said, which showed that, although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype (N. Engl. J. Med. 2010; 363:1128-38).

Frequent exacerbators have higher-stage COPD, more severe obstruction, and more hospitalizations, Dr. Hanania noted.

In addition, the ECLIPSE investigators found that, in 2,138 patients, frequent exacerbator types had an odds ratio of 5.72 of having had an exacerbation in the previous year

Although there other risk factors implicating this phenotype, "the most important question to ask the patient is whether they have had an exacerbation in the previous year," he said. Chronic cough is another factor.

The clinical benefit to identifying the frequent exacerbator, according to Dr. Hanania, is that this group has a greater range of comorbidities, including more inflammation, heightened viral susceptibility, and increased cardiovascular risk, among other susceptibilities.

Using CT for phenotyping

Noting that radiologic phenotyping in COPD is more advanced than in asthma at this time, Dr. Hanania said that quantitative and visual assessment of CT radiographs is "promising" and has helped identify COPD subphenotypes such as emphysema because of accurate assessment of lung inflation, wall thickness, and other factors.

Identifying patients with bronchiectasis, pulmonary arterial enlargement, and acute exacerbations in COPD is also possible with CT radiography, making it possible to predict the different outcomes in each situation. "The clinical implication is that these patients tend to have more frequent exacerbation, worse lung function, and infection," he said, noting that nascent research using imaging to determine biomarkers in functional small airways disease also is occurring.

Systemic inflammation

In the ECLIPSE study, 2,164 COPD patients had an odds ratio of 2.23 for being a current smoker and had higher levels of inflammation, as determined using biomarkers such as C-reactive protein, compared with 337 smokers without COPD and 245 nonsmokers. At the 3-year follow-up, this group with persistently higher inflammation also was classified as having significantly higher all-cause mortality than the group with less inflammation (13% vs. 2%); exacerbation rates in this group were also persistently higher (1.5 vs. 0.9) (PLoS ONE 2012;7:e37483).

Therapeutic implications

Coupling these phenotypes with molecular descriptions of mechanisms and their underlying pathologies can lead to accurate, personalized treatment of COPD. "Phenotypes without clear implications for prognosis and treatment are of little clinical use," Dr. Hanania said, noting that longitudinal studies to validate these phenotypes are necessary.

"Research can help identify mechanisms and courses in different phenotypes, including gender differences," he concluded. "Examining therapeutic responses to different phenotypes can lead to future interventions."

Dr. Hanania disclosed several relationships with a variety of pharmaceutical and medical manufacturers, including Genentech, GlaxoSmithKline* and Astra Zeneca.

Beyond GOLD: A tale of two COPD guidelines

Both address severity and comorbidity, but only one COPD guideline takes into account the latest research on phenotyping in chronic obstructive pulmonary disease.

"The GOLD guidelines do not include clinical phenotypes," said Dr. Joan Soriano, a presenter at the meeting. "But the Spanish ones do."

In fact, there is really only one area where the two documents overlap, said Dr. Soriano: how they define COPD, and even that is not the same. "They both mention the fundamental aspect, which is airflow limitation, and also that the mechanism involved is inflammation," he said. The GOLD definition, however, recognizes the importance of comorbidities, which the Spanish guidelines address the role of tobacco and symptomology.

GOLD (Global Initiative for Chronic Obstructive Lung Disease) is an organization of health care professionals from around the world. "I am not a member of GOLD," Dr. Soriano told the packed session.

The Spanish guidelines are issued by SEPAR, the Spanish Society for Pneumology and Thoracic Surgery. Dr. Soriano is the director of epidemiology and clinical research at the International Center of Advanced Respiratory Medicine (CIMERA) in Palma, Spain.

How the two approach diagnosis also differs. The Spanish guidelines begin with the general COPD diagnosis, then move to the characterization and phenotype, then move to the severity of the disease. They are more specific about age (over 35 years), and have lower limit of normal (LLN) values for persons aged over 70 years and less than 50 years. The GOLD guidelines do not address LLN.

To characterize the disease specifically, the Spanish guidelines address the existence of phenotypes, according to Dr. Soriano, beginning with determining the frequency of exacerbation the patient has per year, and then classifying them eventually into four types: mixed, chronic bronchitis, emphysema, and exacerbator. The GOLD guidelines do not mention phenotypes.

When it comes to the multidimensional assessment of COPD, "the GOLD guidelines lump the mild with the severe spirometry. This is very hard for me to understand," he said. Other classification divergence includes that the Spanish guidelines consider the BODE index.

Treatment in the two guidelines begins similarly, but vectors off from there. "Basically, we are looking at the same trials, so the initial treatments should be short-acting bronchodilators," Dr. Soriano said, but because phenotyping allows for more targeted treatment, the Spanish guidelines offer more detailed treatment options.

In a paper coauthored by Dr. Soriano earlier this year, specific treatment per phenotype included phosphodiesterase-4 inhibitors only for those with chronic bronchitis, inhaled corticosteroids for overlap COPD-asthma, and bronchodilators for infrequent exacerbators (Eur. Respir. J. 2013;41:1252-6).

In the end, the guidelines might not follow the same trajectory, but each has value, he said. "Whatever guidelines you choose, don’t go back and forth. Pick one and use them."

Dr. Soriano reported relationships with Novartis Spain, AstraZeneca, Pfizer, and several other pharmaceutical and medical manufacturers.

wmcknight@frontlinemedcom.com

*CORRECTION, 2/20/2014: An earlier version of this story misstated the name of GlaxoSmithKline.

CHICAGO – Low doses of opioids titrated based on patient ratings of breathing difficulty are effective in managing refractory dyspnea, according to Dr. Donald Mahler.

Because refractory dyspnea is a neuromechanical dissociation, treating more than the pulmonary system can be beneficial, Dr. Mahler said at the annual meeting of the American College of Chest Physicians. "We have targets for the lungs to relieve dyspnea, but we may also have potential targets in the central nervous system that may also provide benefit."

Referring to published data from two randomized controlled studies about the effect of naloxone on blocking opioid signals in patients with COPD who reported breathlessness and perceived "unpleasantness" of dyspnea after exercise, Dr. Mahler said that endogenous opioids modulate the perception of dyspnea; exogenous opioids could therefore do the same (Eur. Respir. J. 2009;33:771-7 and COPD 2011;8:160-6).

Opioid receptors in the limbic system have 100 times greater binding density in the bronchioles and alveolar walls. "That may play a role when thinking about a nebulized approach," said Dr. Mahler of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. The number of side effects, including constipation, was lower with this approach, he added.

Because opioids are known to decrease respiratory drive, there is a "presumable" effect on corollary discharge, which can lead to less perception of breathlessness, according to Dr. Mahler. Narcotics’ dulling effect on the perception of pain and anxiety might also contribute. "Maybe by relieving symptoms, there’s less anxiety as a result," said Dr. Mahler.

He addressed concerns over the "double effect" whereby opioids used to lessen symptoms might actually hasten death in a patient with refractory dyspnea, saying the studies "don’t really support that." Dr. Mahler cited data indicating that higher doses of benzodiazepines used in withdrawal of life-sustaining treatment were not associated with a decreased time from withdrawal of life support to death (CHEST 2004;126:286-93).

As for respiratory depression, Dr. Mahler said he had reviewed 11 studies and found only one report of any change in oxygen saturation after opioid administration.

In deciding whether a patient should be given opioid therapy, Dr. Mahler said physicians should be sure that standard therapies are inadequate and that the risk/benefit ratio favors trial treatment. Establishing treatment goals and confirming that the patient and/or the patient’s family are on board with a trial of opioid treatment is key, he added.

To determine titration, physicians should ask the patients to rate their breathing difficulty. "This is a critical part of the assessment," said Dr. Mahler, noting that the level of breathlessness determines the dose and duration of action.

If dyspnea is episodic, he said, "it doesn’t make sense to administer a long-acting opioid" and so an immediate-release or short-acting form should be considered. If it’s constant, sustained release may be effective, he said.

Dr. Mahler, who said his presentation was related to the off-label use of morphine only, said that the important thing is to "titrate the opioid to achieve the lower effective dose based on the patient’s rating of the dyspnea." Adding an anxiolytic could also be considered, he said. "It’s pretty straightforward that you should discontinue the opioid if there is an unsatisfactory response or if there is an adverse effect."

Dr. Mahler disclosed ties with numerous pharmaceutical manufacturers and other medical organizations, including GlaxoSmithKline, Novartis, and Sunovion.

wmcknight@frontlinemedcom.com

CHICAGO – Low doses of opioids titrated based on patient ratings of breathing difficulty are effective in managing refractory dyspnea, according to Dr. Donald Mahler.

Because refractory dyspnea is a neuromechanical dissociation, treating more than the pulmonary system can be beneficial, Dr. Mahler said at the annual meeting of the American College of Chest Physicians. "We have targets for the lungs to relieve dyspnea, but we may also have potential targets in the central nervous system that may also provide benefit."

Referring to published data from two randomized controlled studies about the effect of naloxone on blocking opioid signals in patients with COPD who reported breathlessness and perceived "unpleasantness" of dyspnea after exercise, Dr. Mahler said that endogenous opioids modulate the perception of dyspnea; exogenous opioids could therefore do the same (Eur. Respir. J. 2009;33:771-7 and COPD 2011;8:160-6).

Opioid receptors in the limbic system have 100 times greater binding density in the bronchioles and alveolar walls. "That may play a role when thinking about a nebulized approach," said Dr. Mahler of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. The number of side effects, including constipation, was lower with this approach, he added.

Because opioids are known to decrease respiratory drive, there is a "presumable" effect on corollary discharge, which can lead to less perception of breathlessness, according to Dr. Mahler. Narcotics’ dulling effect on the perception of pain and anxiety might also contribute. "Maybe by relieving symptoms, there’s less anxiety as a result," said Dr. Mahler.

He addressed concerns over the "double effect" whereby opioids used to lessen symptoms might actually hasten death in a patient with refractory dyspnea, saying the studies "don’t really support that." Dr. Mahler cited data indicating that higher doses of benzodiazepines used in withdrawal of life-sustaining treatment were not associated with a decreased time from withdrawal of life support to death (CHEST 2004;126:286-93).

As for respiratory depression, Dr. Mahler said he had reviewed 11 studies and found only one report of any change in oxygen saturation after opioid administration.

In deciding whether a patient should be given opioid therapy, Dr. Mahler said physicians should be sure that standard therapies are inadequate and that the risk/benefit ratio favors trial treatment. Establishing treatment goals and confirming that the patient and/or the patient’s family are on board with a trial of opioid treatment is key, he added.

To determine titration, physicians should ask the patients to rate their breathing difficulty. "This is a critical part of the assessment," said Dr. Mahler, noting that the level of breathlessness determines the dose and duration of action.

If dyspnea is episodic, he said, "it doesn’t make sense to administer a long-acting opioid" and so an immediate-release or short-acting form should be considered. If it’s constant, sustained release may be effective, he said.

Dr. Mahler, who said his presentation was related to the off-label use of morphine only, said that the important thing is to "titrate the opioid to achieve the lower effective dose based on the patient’s rating of the dyspnea." Adding an anxiolytic could also be considered, he said. "It’s pretty straightforward that you should discontinue the opioid if there is an unsatisfactory response or if there is an adverse effect."

Dr. Mahler disclosed ties with numerous pharmaceutical manufacturers and other medical organizations, including GlaxoSmithKline, Novartis, and Sunovion.

wmcknight@frontlinemedcom.com

CHICAGO – Low doses of opioids titrated based on patient ratings of breathing difficulty are effective in managing refractory dyspnea, according to Dr. Donald Mahler.

Because refractory dyspnea is a neuromechanical dissociation, treating more than the pulmonary system can be beneficial, Dr. Mahler said at the annual meeting of the American College of Chest Physicians. "We have targets for the lungs to relieve dyspnea, but we may also have potential targets in the central nervous system that may also provide benefit."

Referring to published data from two randomized controlled studies about the effect of naloxone on blocking opioid signals in patients with COPD who reported breathlessness and perceived "unpleasantness" of dyspnea after exercise, Dr. Mahler said that endogenous opioids modulate the perception of dyspnea; exogenous opioids could therefore do the same (Eur. Respir. J. 2009;33:771-7 and COPD 2011;8:160-6).

Opioid receptors in the limbic system have 100 times greater binding density in the bronchioles and alveolar walls. "That may play a role when thinking about a nebulized approach," said Dr. Mahler of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. The number of side effects, including constipation, was lower with this approach, he added.

Because opioids are known to decrease respiratory drive, there is a "presumable" effect on corollary discharge, which can lead to less perception of breathlessness, according to Dr. Mahler. Narcotics’ dulling effect on the perception of pain and anxiety might also contribute. "Maybe by relieving symptoms, there’s less anxiety as a result," said Dr. Mahler.

He addressed concerns over the "double effect" whereby opioids used to lessen symptoms might actually hasten death in a patient with refractory dyspnea, saying the studies "don’t really support that." Dr. Mahler cited data indicating that higher doses of benzodiazepines used in withdrawal of life-sustaining treatment were not associated with a decreased time from withdrawal of life support to death (CHEST 2004;126:286-93).

As for respiratory depression, Dr. Mahler said he had reviewed 11 studies and found only one report of any change in oxygen saturation after opioid administration.

In deciding whether a patient should be given opioid therapy, Dr. Mahler said physicians should be sure that standard therapies are inadequate and that the risk/benefit ratio favors trial treatment. Establishing treatment goals and confirming that the patient and/or the patient’s family are on board with a trial of opioid treatment is key, he added.

To determine titration, physicians should ask the patients to rate their breathing difficulty. "This is a critical part of the assessment," said Dr. Mahler, noting that the level of breathlessness determines the dose and duration of action.

If dyspnea is episodic, he said, "it doesn’t make sense to administer a long-acting opioid" and so an immediate-release or short-acting form should be considered. If it’s constant, sustained release may be effective, he said.

Dr. Mahler, who said his presentation was related to the off-label use of morphine only, said that the important thing is to "titrate the opioid to achieve the lower effective dose based on the patient’s rating of the dyspnea." Adding an anxiolytic could also be considered, he said. "It’s pretty straightforward that you should discontinue the opioid if there is an unsatisfactory response or if there is an adverse effect."

Dr. Mahler disclosed ties with numerous pharmaceutical manufacturers and other medical organizations, including GlaxoSmithKline, Novartis, and Sunovion.

wmcknight@frontlinemedcom.com

CHICAGO – The antianginal drug ranolazine improved hemodynamics and functional status in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction in a proof-of-concept trial of just 10 patients.

Six months of twice-daily ranolazine (Ranexa) decreased baseline mean pulmonary arterial pressure (PAP) by 41% and mean pulmonary capillary wedge pressure (PCWP) by 40% in this hard-to-treat population.

Half of the patients improved from World Health Organization functional class III to II, and no patient deteriorated.

"This pilot study suggests ranolazine might be a promising treatment for pulmonary hypertension associated with heart failure with preserved EF [ejection fraction]," Dr. Harrison Farber said during a late-breaking abstract session at the annual meeting of the American College of Chest Physicians.

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, but currently no effective treatment exists for HFpEF alone or PH associated with it. Disappointing results were reported earlier this year for sildenafil (Viagra) in patients with diastolic heart failure in the RELAX trial.

"This pilot study suggests ranolazine might be a promising treatment for pulmonary hypertension associated with heart failure with preserved EF [ejection fraction]..."

Ranolazine is approved for the treatment of chronic angina, and was selected because animal and human data suggest it reduces left ventricular wall stiffness and mechanical dysfunction in conditions associated with diastolic dysfunction, said Dr. Farber, director of the pulmonary hypertension center, Boston University.

To ensure patients in the single-center, open-label, prospective, non–placebo controlled trial truly had HFpEF, entry criteria were fairly strict. They included left ventricular ejection fraction (LVEF) greater than 50% by echocardiogram, mean PAP of at least 25 mm Hg, PCWP between 18 mm Hg and 30 mm Hg, and a pulmonary arterial diastolic pressure-PCWP gradient of 10 mm Hg or less.

The eight women and two men received twice-daily ranolazine 500 mg, titrated to 1,000 mg twice daily, as tolerated. Their mean age was 63 years, mean body mass index 41.6 kg/m², and 80% had diabetes.

At 6 months, mean PAP dropped from 39 mm Hg to 23 mm Hg, mean PCWP from 22 mm Hg to 13 mm HG, and 6-minute walk distances increased from 286 meters to 319 meters, Dr. Farber said.

"Seven of the subjects have actually continued ranolazine for a year or greater and the 6-minute-walk and functional class improvements have actually been maintained to this point," he said.

No significant changes were seen in cardiac index, pulmonary vascular resistance, echocardiogram parameters, brain natriuretic peptide, N-terminal pro-BNP, or troponin.

There was, however, a significant reduction in LV mass at 6 months on blinded MRI evaluation, and a trend for improved right ventricular ejection fraction and decrease in RV mass, he said.

Session comoderator Dr. Namita Sood with Ohio State University in Columbus congratulated the authors on "a courageous study" in an understudied population and asked whether the drop in PAP and PCWP was a consequence of improved LV and diastolic dysfunction or whether ranolazine may have a direct effect on pulmonary vasculature.

Dr. Farber responded, "To be honest, the answer is I don’t know, but since the two were sort of in concert, my guess would be – although it was a small study and I can’t tell you for sure – it was more of an effect on the left ventricle and a concomitant drop in the pulmonary pressures."

Some audience members questioned whether the investigators targeted the right population since patients did not appear to be sufficiently diuresed at entry. Dr. Farber said the exploratory analysis was done to determine if a signal was present and that tighter controls would be needed if they go forward. Diuretics were not controlled in the 10 patients, although no dramatic changes in doses occurred. No patients were on nitrates.

One patient discontinued treatment because of the worsening of an existing symptomatic bradyarrhythmia. Otherwise, the drug was well tolerated, with the only other side effect being headache that went away in the first week of treatment, he said.

Dr. Farber and his coauthors reported grant support from Gilead Sciences, which makes ranolazine.

pwendling@frontlinemedcom.com

This article was updated 11/7/13.

CHICAGO – The antianginal drug ranolazine improved hemodynamics and functional status in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction in a proof-of-concept trial of just 10 patients.

Six months of twice-daily ranolazine (Ranexa) decreased baseline mean pulmonary arterial pressure (PAP) by 41% and mean pulmonary capillary wedge pressure (PCWP) by 40% in this hard-to-treat population.

Half of the patients improved from World Health Organization functional class III to II, and no patient deteriorated.

"This pilot study suggests ranolazine might be a promising treatment for pulmonary hypertension associated with heart failure with preserved EF [ejection fraction]," Dr. Harrison Farber said during a late-breaking abstract session at the annual meeting of the American College of Chest Physicians.

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, but currently no effective treatment exists for HFpEF alone or PH associated with it. Disappointing results were reported earlier this year for sildenafil (Viagra) in patients with diastolic heart failure in the RELAX trial.

"This pilot study suggests ranolazine might be a promising treatment for pulmonary hypertension associated with heart failure with preserved EF [ejection fraction]..."

Ranolazine is approved for the treatment of chronic angina, and was selected because animal and human data suggest it reduces left ventricular wall stiffness and mechanical dysfunction in conditions associated with diastolic dysfunction, said Dr. Farber, director of the pulmonary hypertension center, Boston University.

To ensure patients in the single-center, open-label, prospective, non–placebo controlled trial truly had HFpEF, entry criteria were fairly strict. They included left ventricular ejection fraction (LVEF) greater than 50% by echocardiogram, mean PAP of at least 25 mm Hg, PCWP between 18 mm Hg and 30 mm Hg, and a pulmonary arterial diastolic pressure-PCWP gradient of 10 mm Hg or less.

The eight women and two men received twice-daily ranolazine 500 mg, titrated to 1,000 mg twice daily, as tolerated. Their mean age was 63 years, mean body mass index 41.6 kg/m², and 80% had diabetes.

At 6 months, mean PAP dropped from 39 mm Hg to 23 mm Hg, mean PCWP from 22 mm Hg to 13 mm HG, and 6-minute walk distances increased from 286 meters to 319 meters, Dr. Farber said.

"Seven of the subjects have actually continued ranolazine for a year or greater and the 6-minute-walk and functional class improvements have actually been maintained to this point," he said.

No significant changes were seen in cardiac index, pulmonary vascular resistance, echocardiogram parameters, brain natriuretic peptide, N-terminal pro-BNP, or troponin.

There was, however, a significant reduction in LV mass at 6 months on blinded MRI evaluation, and a trend for improved right ventricular ejection fraction and decrease in RV mass, he said.

Session comoderator Dr. Namita Sood with Ohio State University in Columbus congratulated the authors on "a courageous study" in an understudied population and asked whether the drop in PAP and PCWP was a consequence of improved LV and diastolic dysfunction or whether ranolazine may have a direct effect on pulmonary vasculature.

Dr. Farber responded, "To be honest, the answer is I don’t know, but since the two were sort of in concert, my guess would be – although it was a small study and I can’t tell you for sure – it was more of an effect on the left ventricle and a concomitant drop in the pulmonary pressures."

Some audience members questioned whether the investigators targeted the right population since patients did not appear to be sufficiently diuresed at entry. Dr. Farber said the exploratory analysis was done to determine if a signal was present and that tighter controls would be needed if they go forward. Diuretics were not controlled in the 10 patients, although no dramatic changes in doses occurred. No patients were on nitrates.

One patient discontinued treatment because of the worsening of an existing symptomatic bradyarrhythmia. Otherwise, the drug was well tolerated, with the only other side effect being headache that went away in the first week of treatment, he said.

Dr. Farber and his coauthors reported grant support from Gilead Sciences, which makes ranolazine.

pwendling@frontlinemedcom.com

This article was updated 11/7/13.

CHICAGO – The antianginal drug ranolazine improved hemodynamics and functional status in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction in a proof-of-concept trial of just 10 patients.

Six months of twice-daily ranolazine (Ranexa) decreased baseline mean pulmonary arterial pressure (PAP) by 41% and mean pulmonary capillary wedge pressure (PCWP) by 40% in this hard-to-treat population.

Half of the patients improved from World Health Organization functional class III to II, and no patient deteriorated.

"This pilot study suggests ranolazine might be a promising treatment for pulmonary hypertension associated with heart failure with preserved EF [ejection fraction]," Dr. Harrison Farber said during a late-breaking abstract session at the annual meeting of the American College of Chest Physicians.

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, but currently no effective treatment exists for HFpEF alone or PH associated with it. Disappointing results were reported earlier this year for sildenafil (Viagra) in patients with diastolic heart failure in the RELAX trial.

"This pilot study suggests ranolazine might be a promising treatment for pulmonary hypertension associated with heart failure with preserved EF [ejection fraction]..."

Ranolazine is approved for the treatment of chronic angina, and was selected because animal and human data suggest it reduces left ventricular wall stiffness and mechanical dysfunction in conditions associated with diastolic dysfunction, said Dr. Farber, director of the pulmonary hypertension center, Boston University.

To ensure patients in the single-center, open-label, prospective, non–placebo controlled trial truly had HFpEF, entry criteria were fairly strict. They included left ventricular ejection fraction (LVEF) greater than 50% by echocardiogram, mean PAP of at least 25 mm Hg, PCWP between 18 mm Hg and 30 mm Hg, and a pulmonary arterial diastolic pressure-PCWP gradient of 10 mm Hg or less.

The eight women and two men received twice-daily ranolazine 500 mg, titrated to 1,000 mg twice daily, as tolerated. Their mean age was 63 years, mean body mass index 41.6 kg/m², and 80% had diabetes.

At 6 months, mean PAP dropped from 39 mm Hg to 23 mm Hg, mean PCWP from 22 mm Hg to 13 mm HG, and 6-minute walk distances increased from 286 meters to 319 meters, Dr. Farber said.

"Seven of the subjects have actually continued ranolazine for a year or greater and the 6-minute-walk and functional class improvements have actually been maintained to this point," he said.

No significant changes were seen in cardiac index, pulmonary vascular resistance, echocardiogram parameters, brain natriuretic peptide, N-terminal pro-BNP, or troponin.

There was, however, a significant reduction in LV mass at 6 months on blinded MRI evaluation, and a trend for improved right ventricular ejection fraction and decrease in RV mass, he said.

Session comoderator Dr. Namita Sood with Ohio State University in Columbus congratulated the authors on "a courageous study" in an understudied population and asked whether the drop in PAP and PCWP was a consequence of improved LV and diastolic dysfunction or whether ranolazine may have a direct effect on pulmonary vasculature.

Dr. Farber responded, "To be honest, the answer is I don’t know, but since the two were sort of in concert, my guess would be – although it was a small study and I can’t tell you for sure – it was more of an effect on the left ventricle and a concomitant drop in the pulmonary pressures."

Some audience members questioned whether the investigators targeted the right population since patients did not appear to be sufficiently diuresed at entry. Dr. Farber said the exploratory analysis was done to determine if a signal was present and that tighter controls would be needed if they go forward. Diuretics were not controlled in the 10 patients, although no dramatic changes in doses occurred. No patients were on nitrates.

One patient discontinued treatment because of the worsening of an existing symptomatic bradyarrhythmia. Otherwise, the drug was well tolerated, with the only other side effect being headache that went away in the first week of treatment, he said.

Dr. Farber and his coauthors reported grant support from Gilead Sciences, which makes ranolazine.

pwendling@frontlinemedcom.com

This article was updated 11/7/13.

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

pwendling@frontlinemedcom.com

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

pwendling@frontlinemedcom.com

CHICAGO – One in three patients sent to surgery for a suspicious lung nodule by their community pulmonologist did not have cancer in a retrospective analysis of 385 patients.

In addition, half of patients with benign disease underwent an invasive procedure, Dr. Nichole Tanner said at the annual meeting of the American College of Chest Physicians (ACCP).

Physician judgment plays a key role in the newly updated ACCP lung cancer guidelines (Chest 2013;143:e93S-e120S). They recommend that clinicians estimate the pretest probability of malignancy for indeterminate nodules larger than 8 mm either qualitatively by using their clinical judgment and/or quantitatively with a validated risk model.

Patients in the study, conducted at 16 sites across the country, had 8- to 20-mm nodules, and were mostly former (45%) or current smokers (27.5%), white (86%), and covered by private insurance (55.3%) or Medicare (38.2%). Their average age was 64.5 years.

Invasive procedures included anything outside of simple imaging for monitoring. Computed tomography (CT)- and bronchoscopic-guided biopsy were considered minor invasive procedures, while major invasive procedures included any surgical procedure such as mediastinoscopy, thoracotomy, and video-assisted thorascopic surgery (VATS).

Monitoring only was used for 184 patients, and ran the gamut from one to a "shocking seven" CT or positron-emission tomography (PET) scans in 2 years, said Dr. Tanner, with the Medical University of South Carolina, Charleston. None of these nodules were malignant.

Of the 124 nodules biopsied, 35% were malignant, 56% were diagnosed as benign, and 8% were benign based on stability.

Of the 77 nodules surgically removed, 64% were malignant and 36% were benign, she said.

While a reassuring 76% of nodules seen by community pulmonologists were benign, the results highlight the complexity involved in managing a patient population that is surely on the rise as lung cancer screening spreads nationally.

During a rousing debate that followed the presentation, audience members expressed concern over the 36% of patients taken to surgery for benign disease, highlighting a 3% death rate associated with thoracotomy and the potential for reduced lung function after surgery.

Others, including a thoracic surgeon, countered that removal of a suspicious nodule can catch lung disease at an earlier stage, eliminates the need for repeat CT/PET imaging exposure, and is requested by some patients for their peace of mind or even to pass a pre-employment physical.

Session comoderator and interventional respirologist Dr. Anne Gonzalez, with McGill University Health Center, Montreal, said in an interview, "I was perhaps shocked there were so many [patients] that went directly to surgery, but on the other hand, the guidelines do recommend that if the suspicion of lung cancer is high enough – 65% – patients should go to surgery."

Dr. Gonzalez also echoed comments from the floor that, importantly, the study failed to detail whether patients’ nodules were identified as incidental findings or were the result of symptom-driven screening.

In a multivariate analysis, current smoking (odds ratio, 3.28) and larger nodule size (12-15 mm: OR, 3.30; 16-20 mm: OR, 4.97) influenced who underwent invasive procedures, Dr. Tanner said. Geographic region of the country did not pan out as a predictor.

Cancer was present in 39% of 16- to 20-mm nodules and 31% of 12- to 15-mm nodules, compared with 12% of 8- to 11-mm nodules.

One attendee commented that the number of patients undergoing surgery for benign disease at his institution has dramatically declined with the establishment of a 45-member multidisciplinary tumor board to review and manage patients with lung nodules.

This approach is helpful in that patients won’t be lost to follow-up and can be presented with a plan that has the support of multiple physicians, but "I don’t see this as a feasible way with which to manage every pulmonary nodule," Dr. Tanner said in an interview. "In the lung cancer screening program we’re implementing at our Veterans Affairs hospital in the very near future, we will have a nodule tracking system to ensure that no patients are lost to follow-up and will make treatment and diagnostic decisions based on the Fleischner criteria for radiographic follow-up of lung nodules, as well as the ACCP guidelines."

Dr. Tanner reported consulting for the study sponsor, Integrated Diagnostics.

pwendling@frontlinemedcom.com

CHICAGO – Americans turning to a hospital website for tips on how to quit smoking have only roughly a 50-50 chance of finding help, a study suggests.

In the study, the percentage of hospitals with smoking cessation information easily available on their website was 48% in 2012, up from 28% in 2000. Two analyses were of the same 50 randomly selected U.S. hospitals, with two websites going offline in the interim.

Patrice Wendling/IMNG Medical Media

"This small sample shows there’s a trend toward improvement in hospitals providing information on their websites, with still some opportunity for improvement," Dr. John T. Denny said at the annual meeting of the American College of Chest Physicians.

Session comoderator Dr. Mary Beth Scholand put it more succinctly, saying, "Why there isn’t something there really boggles the mind." Dr. Scholand is director of the interstitial lung disease clinic at University of Utah Health Care in St. Lake City.

The number of consumers visiting the Internet to gather health information has increased dramatically over the last decade, with many searching hospital sites specifically for smoking cessation information and services, said Dr. Denny, who is with the Rutgers-Robert Wood Johnson Medical School in New Brunswick, N.J.

A recent survey reported that 47% of 1,128 adult smokers in England were interested in trying an Internet site or mobile app to quit smoking, though only 0.3% had done so within the past year (J. Med. Internet Res. 2013;15:e50 [doi: 10.2196/jmir.2342]). Interested smokers were younger, more cigarette dependent, had more recent quit attempts, and were more likely to have handheld computer access.

U.S. smokers using the Internet in an analysis of the 2003 Health Information National Trends Survey were also younger and had a higher income, fewer barriers to health care, and a greater interest in quitting than smokers not on the Internet (Nicotine Tob. Res. 2006;8 Suppl 1:S77-85), Dr. Denny observed.

"This is an opportunity for hospitals to actually recruit those folks into their hospital network" at a young age and maintain them as lifelong patients, he said, adding that this "stickiness" or loyalty has already been demonstrated with hospital ob.gyn. services.

Smokers appear to be discerning, however, when it comes to the quality of health information available on the Internet. When 706 current and former smokers in the United States rated 133 different smoking cessation websites, two of the three most frequently visited sites were owned by tobacco companies. These sites were not perceived as helpful, while the nonprofit smokefree.gov and anti-smoking.org received above-average marks (Nicotine Tob. Res. 2006;8 Suppl 1:S27-34).

Dr. Denny and his colleagues did not examine why the hospitals in their analysis failed to provide online resources, although the cost to do so is nominal.

"One feature that’s very, very cost effective is just to add a link to something like QuitNet.com or the American Lung Association," he said.

Dr. Denny and his coauthors reported having no financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Americans turning to a hospital website for tips on how to quit smoking have only roughly a 50-50 chance of finding help, a study suggests.

In the study, the percentage of hospitals with smoking cessation information easily available on their website was 48% in 2012, up from 28% in 2000. Two analyses were of the same 50 randomly selected U.S. hospitals, with two websites going offline in the interim.

Patrice Wendling/IMNG Medical Media

"This small sample shows there’s a trend toward improvement in hospitals providing information on their websites, with still some opportunity for improvement," Dr. John T. Denny said at the annual meeting of the American College of Chest Physicians.

Session comoderator Dr. Mary Beth Scholand put it more succinctly, saying, "Why there isn’t something there really boggles the mind." Dr. Scholand is director of the interstitial lung disease clinic at University of Utah Health Care in St. Lake City.

The number of consumers visiting the Internet to gather health information has increased dramatically over the last decade, with many searching hospital sites specifically for smoking cessation information and services, said Dr. Denny, who is with the Rutgers-Robert Wood Johnson Medical School in New Brunswick, N.J.

A recent survey reported that 47% of 1,128 adult smokers in England were interested in trying an Internet site or mobile app to quit smoking, though only 0.3% had done so within the past year (J. Med. Internet Res. 2013;15:e50 [doi: 10.2196/jmir.2342]). Interested smokers were younger, more cigarette dependent, had more recent quit attempts, and were more likely to have handheld computer access.

U.S. smokers using the Internet in an analysis of the 2003 Health Information National Trends Survey were also younger and had a higher income, fewer barriers to health care, and a greater interest in quitting than smokers not on the Internet (Nicotine Tob. Res. 2006;8 Suppl 1:S77-85), Dr. Denny observed.

"This is an opportunity for hospitals to actually recruit those folks into their hospital network" at a young age and maintain them as lifelong patients, he said, adding that this "stickiness" or loyalty has already been demonstrated with hospital ob.gyn. services.

Smokers appear to be discerning, however, when it comes to the quality of health information available on the Internet. When 706 current and former smokers in the United States rated 133 different smoking cessation websites, two of the three most frequently visited sites were owned by tobacco companies. These sites were not perceived as helpful, while the nonprofit smokefree.gov and anti-smoking.org received above-average marks (Nicotine Tob. Res. 2006;8 Suppl 1:S27-34).

Dr. Denny and his colleagues did not examine why the hospitals in their analysis failed to provide online resources, although the cost to do so is nominal.

"One feature that’s very, very cost effective is just to add a link to something like QuitNet.com or the American Lung Association," he said.

Dr. Denny and his coauthors reported having no financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Americans turning to a hospital website for tips on how to quit smoking have only roughly a 50-50 chance of finding help, a study suggests.

In the study, the percentage of hospitals with smoking cessation information easily available on their website was 48% in 2012, up from 28% in 2000. Two analyses were of the same 50 randomly selected U.S. hospitals, with two websites going offline in the interim.

Patrice Wendling/IMNG Medical Media

"This small sample shows there’s a trend toward improvement in hospitals providing information on their websites, with still some opportunity for improvement," Dr. John T. Denny said at the annual meeting of the American College of Chest Physicians.

Session comoderator Dr. Mary Beth Scholand put it more succinctly, saying, "Why there isn’t something there really boggles the mind." Dr. Scholand is director of the interstitial lung disease clinic at University of Utah Health Care in St. Lake City.

The number of consumers visiting the Internet to gather health information has increased dramatically over the last decade, with many searching hospital sites specifically for smoking cessation information and services, said Dr. Denny, who is with the Rutgers-Robert Wood Johnson Medical School in New Brunswick, N.J.

A recent survey reported that 47% of 1,128 adult smokers in England were interested in trying an Internet site or mobile app to quit smoking, though only 0.3% had done so within the past year (J. Med. Internet Res. 2013;15:e50 [doi: 10.2196/jmir.2342]). Interested smokers were younger, more cigarette dependent, had more recent quit attempts, and were more likely to have handheld computer access.

U.S. smokers using the Internet in an analysis of the 2003 Health Information National Trends Survey were also younger and had a higher income, fewer barriers to health care, and a greater interest in quitting than smokers not on the Internet (Nicotine Tob. Res. 2006;8 Suppl 1:S77-85), Dr. Denny observed.

"This is an opportunity for hospitals to actually recruit those folks into their hospital network" at a young age and maintain them as lifelong patients, he said, adding that this "stickiness" or loyalty has already been demonstrated with hospital ob.gyn. services.

Smokers appear to be discerning, however, when it comes to the quality of health information available on the Internet. When 706 current and former smokers in the United States rated 133 different smoking cessation websites, two of the three most frequently visited sites were owned by tobacco companies. These sites were not perceived as helpful, while the nonprofit smokefree.gov and anti-smoking.org received above-average marks (Nicotine Tob. Res. 2006;8 Suppl 1:S27-34).

Dr. Denny and his colleagues did not examine why the hospitals in their analysis failed to provide online resources, although the cost to do so is nominal.

"One feature that’s very, very cost effective is just to add a link to something like QuitNet.com or the American Lung Association," he said.

Dr. Denny and his coauthors reported having no financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Big Data promises better outcomes and cost savings but begs the question of how much privacy patients are willing to give up.

Via smart phones and cloud computing, hyperspecific information on individual patients can be gathered 24 hours a day, 7 days a week from GPS location, photographs, audio, and other forms of monitoring. Blood pressure, weight, and even pulse detection are already being tracked in some patients. Using advanced algorithms, patient alerts can identify those at risk and possibly allow early interventions that avoid critical events and reduce the cost of care.

"The question is, ‘How much do [patients] want to be monitored?’ " asked Dr. Burt Lesnick, FCCP, of Georgia Pediatric Pulmonary Associates, Atlanta, during a presentation at the annual meeting of the American College of Chest Physicians. Monitoring can assist patients in managing their illness; but empowerment that comes at the cost of constant surveillance "sounds very Orwellian," he said.

Dr. Lesnick has even observed the power of mobile technology to improve asthma control in his own practice. In two small controlled studies, he and his associates randomized a total of 100 children who had asthma and owned a cell phone into three groups. The control group did not receive any communication from the physician. The second group was surveyed by e-mail every 4 days to assess their asthma control scores. If responses indicated an increase in risk, the clinical staff would call the family to discuss the child’s risk status.

The third group also received the rolling assessments, as well as text messages that quizzed their asthma knowledge with true/false questions. Patients who answered the prompts correctly were rewarded with a text message, "You’re right!" and an explanation of why they were correct. If they answered incorrectly, they were told, "Not quite," and also given an explanation.

Dr. Lesnick’s first study included 40 children. In his second study, 60 children were randomized in similar fashion. However, an additional factor – whether patients had public or private insurance – also was used for randomization. Furthermore, the second study addressed whether the success of the combined assessment/knowledge group could be attributed to the increased volume of text messages in that group. The researchers examined whether the text messages created a "reminder" effect for the children to take their medications.

In each study, the groups given rolling assessments and education had significant improvements in forced expiratory flow (FEF25-75%) over baseline measures.

In the first study, the FEF25-75% scores rose from a baseline average of 74.3 plus or minus 31.4 to a poststudy average of 96.0 plus or minus 32.6 in the group given assessments and education. No statistically significant differences in FEF25-75% were seen in the other two groups. In the knowledge-only group, FEF25-75% scores increased from 78.2 plus or minus 32.0 to 84.2 plus or minus 31.7. In the control group, the FEF25-75% scores decreased from 91.1 plus or minus 26.6 to 73.5 plus or minus 27.5.

In the second study, which included equal numbers of children on public and private insurance, the FEF25-75% scores in the education group went from 51.3 plus or minus 21.0 at baseline to 65.5 plus or minus 25.7 at post study.

"Kids were much better reporters of their asthma symptoms with exercise than their parents were," Dr. Lesnick noted. "Not a great surprise, but an important point."

There was a direct correlation between children being put in charge of learning about and managing their asthma, versus relying on their parents to do it for them.

"We were getting them to be empowered ... because we were talking to them in their language: text messages. That’s how they communicate." said Dr. Lesnick.

But how much intrusion will patients be willing to accept in the future to gain "empowerment"? And how much of their information should be shared – and in what manner?

States are eager to use Big Data to drive down health care costs as they compete for federal health dollars based on quality improvements derived from this data, Dr. Lesnick noted. Meanwhile, private insurers are particularly interested in tracking who is most mindful of their health since aggregating this data helps to stratify risk.

Similar to how the auto insurance industry has recognized customers’ willingness to have devices installed in their cars to monitor their driving habits in exchange for lower premiums, health insurers are willing to bank on the notion that people who know they are under observation will change their behavior, Dr. Lesnick said.

Further, Big Data is being driven by health care consumers themselves, particularly younger generations for whom privacy is largely anachronistic, making "patient sensoring" by insurers actually not that hard to achieve, he said.

"There is this psyche out there of people who really want to be monitored," said Dr. Lesnick, citing the ascendency of smartphone watches and humidity sensor apps that allow users to track their exercise performance. These technologies suggest a future of vastly more mobile health or "mHealth" options.

"The Holy Grail is to get the information passively, with sensors all over your body," Dr. Lesnick said.

The encounter between privacy issues and advances in technology begs the questions: If privacy becomes a commodity, will health insurers profit from selling it? And, if our individual data adds to the collective knowledge base, is it our responsibility to give it away for free?

Up-and-coming generations may live according to an ethos whereby "all data should be out there, and it should be completely transparent," Dr. Lesnick said. "But is transparency always a good thing? I don’t know the answer."

wmcknight@frontlinemedcom.com

CHICAGO – Big Data promises better outcomes and cost savings but begs the question of how much privacy patients are willing to give up.

Via smart phones and cloud computing, hyperspecific information on individual patients can be gathered 24 hours a day, 7 days a week from GPS location, photographs, audio, and other forms of monitoring. Blood pressure, weight, and even pulse detection are already being tracked in some patients. Using advanced algorithms, patient alerts can identify those at risk and possibly allow early interventions that avoid critical events and reduce the cost of care.

"The question is, ‘How much do [patients] want to be monitored?’ " asked Dr. Burt Lesnick, FCCP, of Georgia Pediatric Pulmonary Associates, Atlanta, during a presentation at the annual meeting of the American College of Chest Physicians. Monitoring can assist patients in managing their illness; but empowerment that comes at the cost of constant surveillance "sounds very Orwellian," he said.

Dr. Lesnick has even observed the power of mobile technology to improve asthma control in his own practice. In two small controlled studies, he and his associates randomized a total of 100 children who had asthma and owned a cell phone into three groups. The control group did not receive any communication from the physician. The second group was surveyed by e-mail every 4 days to assess their asthma control scores. If responses indicated an increase in risk, the clinical staff would call the family to discuss the child’s risk status.

The third group also received the rolling assessments, as well as text messages that quizzed their asthma knowledge with true/false questions. Patients who answered the prompts correctly were rewarded with a text message, "You’re right!" and an explanation of why they were correct. If they answered incorrectly, they were told, "Not quite," and also given an explanation.

Dr. Lesnick’s first study included 40 children. In his second study, 60 children were randomized in similar fashion. However, an additional factor – whether patients had public or private insurance – also was used for randomization. Furthermore, the second study addressed whether the success of the combined assessment/knowledge group could be attributed to the increased volume of text messages in that group. The researchers examined whether the text messages created a "reminder" effect for the children to take their medications.

In each study, the groups given rolling assessments and education had significant improvements in forced expiratory flow (FEF25-75%) over baseline measures.

In the first study, the FEF25-75% scores rose from a baseline average of 74.3 plus or minus 31.4 to a poststudy average of 96.0 plus or minus 32.6 in the group given assessments and education. No statistically significant differences in FEF25-75% were seen in the other two groups. In the knowledge-only group, FEF25-75% scores increased from 78.2 plus or minus 32.0 to 84.2 plus or minus 31.7. In the control group, the FEF25-75% scores decreased from 91.1 plus or minus 26.6 to 73.5 plus or minus 27.5.

In the second study, which included equal numbers of children on public and private insurance, the FEF25-75% scores in the education group went from 51.3 plus or minus 21.0 at baseline to 65.5 plus or minus 25.7 at post study.

"Kids were much better reporters of their asthma symptoms with exercise than their parents were," Dr. Lesnick noted. "Not a great surprise, but an important point."

There was a direct correlation between children being put in charge of learning about and managing their asthma, versus relying on their parents to do it for them.

"We were getting them to be empowered ... because we were talking to them in their language: text messages. That’s how they communicate." said Dr. Lesnick.

But how much intrusion will patients be willing to accept in the future to gain "empowerment"? And how much of their information should be shared – and in what manner?

States are eager to use Big Data to drive down health care costs as they compete for federal health dollars based on quality improvements derived from this data, Dr. Lesnick noted. Meanwhile, private insurers are particularly interested in tracking who is most mindful of their health since aggregating this data helps to stratify risk.

Similar to how the auto insurance industry has recognized customers’ willingness to have devices installed in their cars to monitor their driving habits in exchange for lower premiums, health insurers are willing to bank on the notion that people who know they are under observation will change their behavior, Dr. Lesnick said.

Further, Big Data is being driven by health care consumers themselves, particularly younger generations for whom privacy is largely anachronistic, making "patient sensoring" by insurers actually not that hard to achieve, he said.

"There is this psyche out there of people who really want to be monitored," said Dr. Lesnick, citing the ascendency of smartphone watches and humidity sensor apps that allow users to track their exercise performance. These technologies suggest a future of vastly more mobile health or "mHealth" options.

"The Holy Grail is to get the information passively, with sensors all over your body," Dr. Lesnick said.

The encounter between privacy issues and advances in technology begs the questions: If privacy becomes a commodity, will health insurers profit from selling it? And, if our individual data adds to the collective knowledge base, is it our responsibility to give it away for free?

Up-and-coming generations may live according to an ethos whereby "all data should be out there, and it should be completely transparent," Dr. Lesnick said. "But is transparency always a good thing? I don’t know the answer."

wmcknight@frontlinemedcom.com

CHICAGO – Big Data promises better outcomes and cost savings but begs the question of how much privacy patients are willing to give up.

Via smart phones and cloud computing, hyperspecific information on individual patients can be gathered 24 hours a day, 7 days a week from GPS location, photographs, audio, and other forms of monitoring. Blood pressure, weight, and even pulse detection are already being tracked in some patients. Using advanced algorithms, patient alerts can identify those at risk and possibly allow early interventions that avoid critical events and reduce the cost of care.

"The question is, ‘How much do [patients] want to be monitored?’ " asked Dr. Burt Lesnick, FCCP, of Georgia Pediatric Pulmonary Associates, Atlanta, during a presentation at the annual meeting of the American College of Chest Physicians. Monitoring can assist patients in managing their illness; but empowerment that comes at the cost of constant surveillance "sounds very Orwellian," he said.

Dr. Lesnick has even observed the power of mobile technology to improve asthma control in his own practice. In two small controlled studies, he and his associates randomized a total of 100 children who had asthma and owned a cell phone into three groups. The control group did not receive any communication from the physician. The second group was surveyed by e-mail every 4 days to assess their asthma control scores. If responses indicated an increase in risk, the clinical staff would call the family to discuss the child’s risk status.

The third group also received the rolling assessments, as well as text messages that quizzed their asthma knowledge with true/false questions. Patients who answered the prompts correctly were rewarded with a text message, "You’re right!" and an explanation of why they were correct. If they answered incorrectly, they were told, "Not quite," and also given an explanation.

Dr. Lesnick’s first study included 40 children. In his second study, 60 children were randomized in similar fashion. However, an additional factor – whether patients had public or private insurance – also was used for randomization. Furthermore, the second study addressed whether the success of the combined assessment/knowledge group could be attributed to the increased volume of text messages in that group. The researchers examined whether the text messages created a "reminder" effect for the children to take their medications.

In each study, the groups given rolling assessments and education had significant improvements in forced expiratory flow (FEF25-75%) over baseline measures.

In the first study, the FEF25-75% scores rose from a baseline average of 74.3 plus or minus 31.4 to a poststudy average of 96.0 plus or minus 32.6 in the group given assessments and education. No statistically significant differences in FEF25-75% were seen in the other two groups. In the knowledge-only group, FEF25-75% scores increased from 78.2 plus or minus 32.0 to 84.2 plus or minus 31.7. In the control group, the FEF25-75% scores decreased from 91.1 plus or minus 26.6 to 73.5 plus or minus 27.5.

In the second study, which included equal numbers of children on public and private insurance, the FEF25-75% scores in the education group went from 51.3 plus or minus 21.0 at baseline to 65.5 plus or minus 25.7 at post study.

"Kids were much better reporters of their asthma symptoms with exercise than their parents were," Dr. Lesnick noted. "Not a great surprise, but an important point."

There was a direct correlation between children being put in charge of learning about and managing their asthma, versus relying on their parents to do it for them.

"We were getting them to be empowered ... because we were talking to them in their language: text messages. That’s how they communicate." said Dr. Lesnick.

But how much intrusion will patients be willing to accept in the future to gain "empowerment"? And how much of their information should be shared – and in what manner?

States are eager to use Big Data to drive down health care costs as they compete for federal health dollars based on quality improvements derived from this data, Dr. Lesnick noted. Meanwhile, private insurers are particularly interested in tracking who is most mindful of their health since aggregating this data helps to stratify risk.

Similar to how the auto insurance industry has recognized customers’ willingness to have devices installed in their cars to monitor their driving habits in exchange for lower premiums, health insurers are willing to bank on the notion that people who know they are under observation will change their behavior, Dr. Lesnick said.

Further, Big Data is being driven by health care consumers themselves, particularly younger generations for whom privacy is largely anachronistic, making "patient sensoring" by insurers actually not that hard to achieve, he said.

"There is this psyche out there of people who really want to be monitored," said Dr. Lesnick, citing the ascendency of smartphone watches and humidity sensor apps that allow users to track their exercise performance. These technologies suggest a future of vastly more mobile health or "mHealth" options.

"The Holy Grail is to get the information passively, with sensors all over your body," Dr. Lesnick said.

The encounter between privacy issues and advances in technology begs the questions: If privacy becomes a commodity, will health insurers profit from selling it? And, if our individual data adds to the collective knowledge base, is it our responsibility to give it away for free?

Up-and-coming generations may live according to an ethos whereby "all data should be out there, and it should be completely transparent," Dr. Lesnick said. "But is transparency always a good thing? I don’t know the answer."

wmcknight@frontlinemedcom.com

Despite some controversy over its efficacy, the biomarker procalcitonin does have a legitimate role to play in helping determine the duration of antibiotic therapy in community-acquired infections, according to a presenter at the annual meeting of the American College of Chest Physicians.

Procalcitonin is a biomarker of inflammation that, like C-reactive protein, is seen at higher levels in patients with bacterial infections. How statistically significant a difference it will make in curbing antibiotic use in a hospital and helping to stratify risk "depends on what your baseline [of antibiotic use] is," said Dr. Richard Wunderink, FCCP, of Northwestern University, Chicago.

Dr. Wunderink cited two meta-analyses, including a Cochrane Database systematic review of patient-level data, that showed "highly statistically significant differences" in the duration of antibiotic therapy when procalcitonin was measured. In the study, 898 out of 999 patients with community-acquired pneumonia were given antibiotics and had their procalcitonin levels measured; the control group, numbering 1,028, was also given antibiotics but did not have procalcitonin levels measured (Cochrane Database Syst. Rev. 2012 Sept. 12;9:CD007498 [doi: 10.1002/14651858.CD007498.pub2]).

The group measured for elevated procalcitonin as a way of determining the course of antibiotic therapy had an average exposure to antibiotics of 6 days, compared with an average exposure of 10 days in the control group.

"It does shorten the course of therapy," said Dr. Wunderink. However, he added, there has been an effort over the past decade in the United States to reduce overall antibiotic therapy as a way to combat antibacterial resistance, so the difference is less than it might be in European countries.

Also important to consider, said Dr. Wunderink, is the ongoing inflammatory response in some patients. "There is a point at which the cytokines response starts to drive the procalcitonin more than the bacteria do ... so at some point, it switches from being a marker of uncontrolled bacterial infection to a marker of uncontrolled inflammation," Dr. Wunderink said.

Another issue, he said, is that physicians "need to be comfortable withholding antibiotics in patients with community-acquired pneumonia," since some patients will not have notably elevated procalcitonin levels, regardless of infection. "It may be that procalcitonin can tell you enough about etiology that you can treat for atypicals, but it’s still to be proven," said Dr. Wunderink.

When there is diagnostic uncertainty, as in a patient who has underlying heart failure and symptoms that may or may not be pneumonia, Dr. Wunderink said that short-course antibiotic therapy, such as 5-7 days, is appropriate.

"But I am not sure that procalcitonin actually decreases that duration of therapy," he said. "It may support the idea of narrower-spectrum atypical antibiotic therapy, but the greatest benefit is in discontinuing the therapy in patients with diagnostic uncertainty."

Dr. Wunderink disclosed that he has received investigator grants from bioMérieux.

wmcknight@frontlinemedcom.com

Despite some controversy over its efficacy, the biomarker procalcitonin does have a legitimate role to play in helping determine the duration of antibiotic therapy in community-acquired infections, according to a presenter at the annual meeting of the American College of Chest Physicians.

Procalcitonin is a biomarker of inflammation that, like C-reactive protein, is seen at higher levels in patients with bacterial infections. How statistically significant a difference it will make in curbing antibiotic use in a hospital and helping to stratify risk "depends on what your baseline [of antibiotic use] is," said Dr. Richard Wunderink, FCCP, of Northwestern University, Chicago.

Dr. Wunderink cited two meta-analyses, including a Cochrane Database systematic review of patient-level data, that showed "highly statistically significant differences" in the duration of antibiotic therapy when procalcitonin was measured. In the study, 898 out of 999 patients with community-acquired pneumonia were given antibiotics and had their procalcitonin levels measured; the control group, numbering 1,028, was also given antibiotics but did not have procalcitonin levels measured (Cochrane Database Syst. Rev. 2012 Sept. 12;9:CD007498 [doi: 10.1002/14651858.CD007498.pub2]).

The group measured for elevated procalcitonin as a way of determining the course of antibiotic therapy had an average exposure to antibiotics of 6 days, compared with an average exposure of 10 days in the control group.

"It does shorten the course of therapy," said Dr. Wunderink. However, he added, there has been an effort over the past decade in the United States to reduce overall antibiotic therapy as a way to combat antibacterial resistance, so the difference is less than it might be in European countries.

Also important to consider, said Dr. Wunderink, is the ongoing inflammatory response in some patients. "There is a point at which the cytokines response starts to drive the procalcitonin more than the bacteria do ... so at some point, it switches from being a marker of uncontrolled bacterial infection to a marker of uncontrolled inflammation," Dr. Wunderink said.

Another issue, he said, is that physicians "need to be comfortable withholding antibiotics in patients with community-acquired pneumonia," since some patients will not have notably elevated procalcitonin levels, regardless of infection. "It may be that procalcitonin can tell you enough about etiology that you can treat for atypicals, but it’s still to be proven," said Dr. Wunderink.

When there is diagnostic uncertainty, as in a patient who has underlying heart failure and symptoms that may or may not be pneumonia, Dr. Wunderink said that short-course antibiotic therapy, such as 5-7 days, is appropriate.

"But I am not sure that procalcitonin actually decreases that duration of therapy," he said. "It may support the idea of narrower-spectrum atypical antibiotic therapy, but the greatest benefit is in discontinuing the therapy in patients with diagnostic uncertainty."

Dr. Wunderink disclosed that he has received investigator grants from bioMérieux.

wmcknight@frontlinemedcom.com

Despite some controversy over its efficacy, the biomarker procalcitonin does have a legitimate role to play in helping determine the duration of antibiotic therapy in community-acquired infections, according to a presenter at the annual meeting of the American College of Chest Physicians.

Procalcitonin is a biomarker of inflammation that, like C-reactive protein, is seen at higher levels in patients with bacterial infections. How statistically significant a difference it will make in curbing antibiotic use in a hospital and helping to stratify risk "depends on what your baseline [of antibiotic use] is," said Dr. Richard Wunderink, FCCP, of Northwestern University, Chicago.

Dr. Wunderink cited two meta-analyses, including a Cochrane Database systematic review of patient-level data, that showed "highly statistically significant differences" in the duration of antibiotic therapy when procalcitonin was measured. In the study, 898 out of 999 patients with community-acquired pneumonia were given antibiotics and had their procalcitonin levels measured; the control group, numbering 1,028, was also given antibiotics but did not have procalcitonin levels measured (Cochrane Database Syst. Rev. 2012 Sept. 12;9:CD007498 [doi: 10.1002/14651858.CD007498.pub2]).

The group measured for elevated procalcitonin as a way of determining the course of antibiotic therapy had an average exposure to antibiotics of 6 days, compared with an average exposure of 10 days in the control group.

"It does shorten the course of therapy," said Dr. Wunderink. However, he added, there has been an effort over the past decade in the United States to reduce overall antibiotic therapy as a way to combat antibacterial resistance, so the difference is less than it might be in European countries.

Also important to consider, said Dr. Wunderink, is the ongoing inflammatory response in some patients. "There is a point at which the cytokines response starts to drive the procalcitonin more than the bacteria do ... so at some point, it switches from being a marker of uncontrolled bacterial infection to a marker of uncontrolled inflammation," Dr. Wunderink said.

Another issue, he said, is that physicians "need to be comfortable withholding antibiotics in patients with community-acquired pneumonia," since some patients will not have notably elevated procalcitonin levels, regardless of infection. "It may be that procalcitonin can tell you enough about etiology that you can treat for atypicals, but it’s still to be proven," said Dr. Wunderink.

When there is diagnostic uncertainty, as in a patient who has underlying heart failure and symptoms that may or may not be pneumonia, Dr. Wunderink said that short-course antibiotic therapy, such as 5-7 days, is appropriate.

"But I am not sure that procalcitonin actually decreases that duration of therapy," he said. "It may support the idea of narrower-spectrum atypical antibiotic therapy, but the greatest benefit is in discontinuing the therapy in patients with diagnostic uncertainty."

Dr. Wunderink disclosed that he has received investigator grants from bioMérieux.

wmcknight@frontlinemedcom.com

CHICAGO – Despite a national downturn in cigarette smoking, a growing number of young Americans are turning to hookah bars to smoke tobacco, a study has shown.

The trend is driven by the social nature of hookah bars and myths about the safety of smoking hookah, also called shisha, narghile, hubble-bubble, and goza, Dr. Srihari Veeraraghavan reported at the annual meeting of the American College of Chest Physicians.

For the first time, a large study showed hookah smoking had eclipsed cigarette smoking for both ever use (46.4% vs. 42.1%) and past-year use (28.4% vs. 19.6%) among 1,203 University of Florida students (BMC Public Health 2013;13:302).

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Patrice Wendling/IMNG Medical Media

More than a third of current cigarette smokers used hookah, but equally worrisome, 29% of current hookah smokers reported never having smoked a cigarette.

"We’ve made impressive strides in the last 40-50 years by reducing smoking in this country," he said in an interview. "And the concern is that students use hookah in their universities, and when they get out in their real life, they’re going to go back to cigarettes because it’s as addictive, if not more [so], than cigarettes."

Myths surrounding hookah/shisha smoking are that it is less addictive, less harmful, and contains less nicotine than conventional cigarettes, said Dr. Veeraraghavan of Emory University in Atlanta.

He highlighted a widely publicized 1997 New York Times article quoting one hookah smoker as saying cigarettes are for "nervous," "competitive" people, but that narghile smoking "teaches you patience and tolerance, and gives you an appreciation of good company."

Some smokers also believe the water in the pipe filters out toxins and that adding molasses or fruit to flavor the tobacco imparts a health benefit.

"Hookah smoking leads to cigarette smoking, and cigarette smokers planning to quit take up hookah thinking that it’s better," Dr. Veeraraghavan said.

Though data in humans are limited, a study found similar peak nicotine concentrations after smoking one cigarette vs. smoking a hookah for a maximum of 45 minutes, but that hookah smoking was associated with greater carbon monoxide levels and 1.7 times the exposure to nicotine (Am. J. Prev. Med. 2009;37:518-23).

A typical hookah session lasts about an hour and may involve 200 puffs. Thus, "in one hookah session, smokers may inhale the equivalent of 100 cigarettes," he said.

This is particularly concerning in light of the recent Canadian Youth Smoking Survey showing that hookah use increased 6% from 2006 through 2010 among kids, grades 9 through 12 (Prev. Chronic Dis. 2013 May 9;10E73). Once again, current cigarette smokers were more likely to use hookahs, but marijuana and alcohol use also predicted hookah use.

Dr. Veeraraghavan suggested that alternative forms of smoking such as hookahs, e-cigarettes, and marijuana should be included in all smoking surveys and that additional research is needed to elucidate the effects on pulmonary function and overall health. Better regulatory mechanisms are also needed, as laws are unclear about hookah smoking in restaurants and other public venues.

Finally, physicians should begin asking patients of all ages about their hookah use since younger adult smokers are less likely to visit the office, but parents will go home and talk to their kids – young or older – about the health risks posed by hookah smoking, he said.

For physicians unaware or uncertain about the emerging popularity of hookah smoking, Dr. Veeraraghavan concluded by showing a slide listing no fewer than 50 hookah bars all in the Chicago area, many not far from CHEST 2013.

Dr. Veeraraghavan reported having no relevant financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Despite a national downturn in cigarette smoking, a growing number of young Americans are turning to hookah bars to smoke tobacco, a study has shown.

The trend is driven by the social nature of hookah bars and myths about the safety of smoking hookah, also called shisha, narghile, hubble-bubble, and goza, Dr. Srihari Veeraraghavan reported at the annual meeting of the American College of Chest Physicians.

For the first time, a large study showed hookah smoking had eclipsed cigarette smoking for both ever use (46.4% vs. 42.1%) and past-year use (28.4% vs. 19.6%) among 1,203 University of Florida students (BMC Public Health 2013;13:302).

<

Patrice Wendling/IMNG Medical Media

More than a third of current cigarette smokers used hookah, but equally worrisome, 29% of current hookah smokers reported never having smoked a cigarette.

"We’ve made impressive strides in the last 40-50 years by reducing smoking in this country," he said in an interview. "And the concern is that students use hookah in their universities, and when they get out in their real life, they’re going to go back to cigarettes because it’s as addictive, if not more [so], than cigarettes."

Myths surrounding hookah/shisha smoking are that it is less addictive, less harmful, and contains less nicotine than conventional cigarettes, said Dr. Veeraraghavan of Emory University in Atlanta.

He highlighted a widely publicized 1997 New York Times article quoting one hookah smoker as saying cigarettes are for "nervous," "competitive" people, but that narghile smoking "teaches you patience and tolerance, and gives you an appreciation of good company."

Some smokers also believe the water in the pipe filters out toxins and that adding molasses or fruit to flavor the tobacco imparts a health benefit.

"Hookah smoking leads to cigarette smoking, and cigarette smokers planning to quit take up hookah thinking that it’s better," Dr. Veeraraghavan said.

Though data in humans are limited, a study found similar peak nicotine concentrations after smoking one cigarette vs. smoking a hookah for a maximum of 45 minutes, but that hookah smoking was associated with greater carbon monoxide levels and 1.7 times the exposure to nicotine (Am. J. Prev. Med. 2009;37:518-23).

A typical hookah session lasts about an hour and may involve 200 puffs. Thus, "in one hookah session, smokers may inhale the equivalent of 100 cigarettes," he said.

This is particularly concerning in light of the recent Canadian Youth Smoking Survey showing that hookah use increased 6% from 2006 through 2010 among kids, grades 9 through 12 (Prev. Chronic Dis. 2013 May 9;10E73). Once again, current cigarette smokers were more likely to use hookahs, but marijuana and alcohol use also predicted hookah use.

Dr. Veeraraghavan suggested that alternative forms of smoking such as hookahs, e-cigarettes, and marijuana should be included in all smoking surveys and that additional research is needed to elucidate the effects on pulmonary function and overall health. Better regulatory mechanisms are also needed, as laws are unclear about hookah smoking in restaurants and other public venues.

Finally, physicians should begin asking patients of all ages about their hookah use since younger adult smokers are less likely to visit the office, but parents will go home and talk to their kids – young or older – about the health risks posed by hookah smoking, he said.

For physicians unaware or uncertain about the emerging popularity of hookah smoking, Dr. Veeraraghavan concluded by showing a slide listing no fewer than 50 hookah bars all in the Chicago area, many not far from CHEST 2013.

Dr. Veeraraghavan reported having no relevant financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Despite a national downturn in cigarette smoking, a growing number of young Americans are turning to hookah bars to smoke tobacco, a study has shown.

The trend is driven by the social nature of hookah bars and myths about the safety of smoking hookah, also called shisha, narghile, hubble-bubble, and goza, Dr. Srihari Veeraraghavan reported at the annual meeting of the American College of Chest Physicians.

For the first time, a large study showed hookah smoking had eclipsed cigarette smoking for both ever use (46.4% vs. 42.1%) and past-year use (28.4% vs. 19.6%) among 1,203 University of Florida students (BMC Public Health 2013;13:302).

<

Patrice Wendling/IMNG Medical Media

More than a third of current cigarette smokers used hookah, but equally worrisome, 29% of current hookah smokers reported never having smoked a cigarette.

"We’ve made impressive strides in the last 40-50 years by reducing smoking in this country," he said in an interview. "And the concern is that students use hookah in their universities, and when they get out in their real life, they’re going to go back to cigarettes because it’s as addictive, if not more [so], than cigarettes."

Myths surrounding hookah/shisha smoking are that it is less addictive, less harmful, and contains less nicotine than conventional cigarettes, said Dr. Veeraraghavan of Emory University in Atlanta.

He highlighted a widely publicized 1997 New York Times article quoting one hookah smoker as saying cigarettes are for "nervous," "competitive" people, but that narghile smoking "teaches you patience and tolerance, and gives you an appreciation of good company."

Some smokers also believe the water in the pipe filters out toxins and that adding molasses or fruit to flavor the tobacco imparts a health benefit.

"Hookah smoking leads to cigarette smoking, and cigarette smokers planning to quit take up hookah thinking that it’s better," Dr. Veeraraghavan said.

Though data in humans are limited, a study found similar peak nicotine concentrations after smoking one cigarette vs. smoking a hookah for a maximum of 45 minutes, but that hookah smoking was associated with greater carbon monoxide levels and 1.7 times the exposure to nicotine (Am. J. Prev. Med. 2009;37:518-23).

A typical hookah session lasts about an hour and may involve 200 puffs. Thus, "in one hookah session, smokers may inhale the equivalent of 100 cigarettes," he said.

This is particularly concerning in light of the recent Canadian Youth Smoking Survey showing that hookah use increased 6% from 2006 through 2010 among kids, grades 9 through 12 (Prev. Chronic Dis. 2013 May 9;10E73). Once again, current cigarette smokers were more likely to use hookahs, but marijuana and alcohol use also predicted hookah use.

Dr. Veeraraghavan suggested that alternative forms of smoking such as hookahs, e-cigarettes, and marijuana should be included in all smoking surveys and that additional research is needed to elucidate the effects on pulmonary function and overall health. Better regulatory mechanisms are also needed, as laws are unclear about hookah smoking in restaurants and other public venues.

Finally, physicians should begin asking patients of all ages about their hookah use since younger adult smokers are less likely to visit the office, but parents will go home and talk to their kids – young or older – about the health risks posed by hookah smoking, he said.

For physicians unaware or uncertain about the emerging popularity of hookah smoking, Dr. Veeraraghavan concluded by showing a slide listing no fewer than 50 hookah bars all in the Chicago area, many not far from CHEST 2013.

Dr. Veeraraghavan reported having no relevant financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Community physicians can feel comfortable diagnosing and treating hypersensitivity pneumonitis, according to a panel of pulmonary experts.

"It’s not always necessary to refer patients to academic centers where the specialists are," said Dr. Karen Patterson, who moderated the panel at the annual meeting of the American College of Chest Physicians. "That’s not always easy for patients, since those centers are often far away from where they live."

The key to accurate diagnosis is taking a thorough clinical history. Sometimes, that means asking family members the same questions asked of the patient, since not everyone recalls the same information, said Dr. Patterson of the Penn Lung Center at the University of Pennsylvania, Philadelphia.

Hypersensitivity pneumonitis is antigen driven, and lymphocytosis is a hallmark, Dr. Patterson said.

The allergens associated with the condition typically come from birds, but apparently not from chickens, according to panelist Dr. Kevin Brown of National Jewish Health in Denver.

Other antigens to ask about include bird products such as down bedding as well as mold and various industrial antigens.

Pulmonary and systemic symptoms can vary in intensity with each patient, Dr. Patterson said. When classifying the disease, it is important to distinguish between fibrotic and nonfibrotic disease. "Fibrotic disease is difficult to diagnose, and is associated with [poorer] outcomes," she said.

Patients present with dyspnea, hypoxemia, and cough as well as systemic manifestations such as fever, myalgia, weight loss, and fatigue.

CT findings are usually more thorough than radiography, said Dr. Patterson, who added that biopsy is necessary on rare occasions.

"Be sure to get all three lobes of the affected lung"; otherwise there will not be enough information to accurately assess the disease, she added.

"Antigen avoidance is the best management of hypersensitivity pneumonitis," according to Dr. Mary Strek of the University of Chicago. "Patients do best when you’ve accurately identified the antigen, and then removed it, although this is not always easy."

Treatment includes corticosteroids, and in some cases, immunosuppressive therapies.

wmcknight@frontlinemedcom.com

CHICAGO – Community physicians can feel comfortable diagnosing and treating hypersensitivity pneumonitis, according to a panel of pulmonary experts.

"It’s not always necessary to refer patients to academic centers where the specialists are," said Dr. Karen Patterson, who moderated the panel at the annual meeting of the American College of Chest Physicians. "That’s not always easy for patients, since those centers are often far away from where they live."

The key to accurate diagnosis is taking a thorough clinical history. Sometimes, that means asking family members the same questions asked of the patient, since not everyone recalls the same information, said Dr. Patterson of the Penn Lung Center at the University of Pennsylvania, Philadelphia.

Hypersensitivity pneumonitis is antigen driven, and lymphocytosis is a hallmark, Dr. Patterson said.

The allergens associated with the condition typically come from birds, but apparently not from chickens, according to panelist Dr. Kevin Brown of National Jewish Health in Denver.

Other antigens to ask about include bird products such as down bedding as well as mold and various industrial antigens.

Pulmonary and systemic symptoms can vary in intensity with each patient, Dr. Patterson said. When classifying the disease, it is important to distinguish between fibrotic and nonfibrotic disease. "Fibrotic disease is difficult to diagnose, and is associated with [poorer] outcomes," she said.

Patients present with dyspnea, hypoxemia, and cough as well as systemic manifestations such as fever, myalgia, weight loss, and fatigue.

CT findings are usually more thorough than radiography, said Dr. Patterson, who added that biopsy is necessary on rare occasions.

"Be sure to get all three lobes of the affected lung"; otherwise there will not be enough information to accurately assess the disease, she added.

"Antigen avoidance is the best management of hypersensitivity pneumonitis," according to Dr. Mary Strek of the University of Chicago. "Patients do best when you’ve accurately identified the antigen, and then removed it, although this is not always easy."

Treatment includes corticosteroids, and in some cases, immunosuppressive therapies.

wmcknight@frontlinemedcom.com

CHICAGO – Community physicians can feel comfortable diagnosing and treating hypersensitivity pneumonitis, according to a panel of pulmonary experts.

"It’s not always necessary to refer patients to academic centers where the specialists are," said Dr. Karen Patterson, who moderated the panel at the annual meeting of the American College of Chest Physicians. "That’s not always easy for patients, since those centers are often far away from where they live."

The key to accurate diagnosis is taking a thorough clinical history. Sometimes, that means asking family members the same questions asked of the patient, since not everyone recalls the same information, said Dr. Patterson of the Penn Lung Center at the University of Pennsylvania, Philadelphia.

Hypersensitivity pneumonitis is antigen driven, and lymphocytosis is a hallmark, Dr. Patterson said.

The allergens associated with the condition typically come from birds, but apparently not from chickens, according to panelist Dr. Kevin Brown of National Jewish Health in Denver.

Other antigens to ask about include bird products such as down bedding as well as mold and various industrial antigens.

Pulmonary and systemic symptoms can vary in intensity with each patient, Dr. Patterson said. When classifying the disease, it is important to distinguish between fibrotic and nonfibrotic disease. "Fibrotic disease is difficult to diagnose, and is associated with [poorer] outcomes," she said.

Patients present with dyspnea, hypoxemia, and cough as well as systemic manifestations such as fever, myalgia, weight loss, and fatigue.

CT findings are usually more thorough than radiography, said Dr. Patterson, who added that biopsy is necessary on rare occasions.

"Be sure to get all three lobes of the affected lung"; otherwise there will not be enough information to accurately assess the disease, she added.

"Antigen avoidance is the best management of hypersensitivity pneumonitis," according to Dr. Mary Strek of the University of Chicago. "Patients do best when you’ve accurately identified the antigen, and then removed it, although this is not always easy."

Treatment includes corticosteroids, and in some cases, immunosuppressive therapies.

wmcknight@frontlinemedcom.com