Brief Report: Increased Cotinine Concentrations are Associated With Reduced Expression of Cathelicidin (LL-37) and NOD-2 in Alveolar Macrophages of PLWH Who Smoke.

There is a strong link between cigarette smoking and pulmonary complications among people living with HIV. However, the effects of smoking on the local lung immune environment in this population remain unclear. Bronchoalveolar lavage and saliva were collected from HIV-infected smokers involved in a prospective study investigating alveolar macrophage expression of host defense molecules. Salivary cotinine concentrations were inversely related to expression of the immune cell receptor nucleotide-binding oligomerization domain-2 and the cathelicidin antimicrobial peptide LL-37. The negative correlation between salivary cotinine and LL-37 was particularly strong. Our study provides insight into how nicotine may adversely affect lung innate immunity in HIV.

Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation.

Rationale: Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC monomers and polymers in lung bronchoalveolar lavage fluid (BALF) might serve as a marker of lung inflammasome activity. Objectives: To determine whether lung ASC concentrations or oligomerization status predicts lung function or activity of lung inflammation. Methods: BALF ASC amount and oligomerization status was studied in three distinct cohorts: (1) young healthy non-smokers, vapers and smokers; (2) healthy HIV+ smokers who underwent detailed lung function studies; and (3) hospitalized patients with suspected pneumonia. We quantified cell free BALF ASC levels by ELISA and immunoblot. Oligomers (i.e., ASC specks) were identified by chemical crosslinking and ability to sediment with centrifugation. Measurement and Main Results: ASC levels are significantly higher in lung lining fluid than in plasma as well as higher in smoker lungs compared to non-smoker lungs. In this context, ASC levels correlate with macrophage numbers, smoking intensity and loss of lung diffusion capacity in a well-characterized cohort of healthy HIV+ smokers. However, only monomeric ASC was found in our BALF samples from all subjects, including patients with lung infections. Conclusions: Even though, most, if not all, extracellular ASC in BALF exists in the soluble, monomeric form, monomeric ASC concentrations still reflect the inflammatory status of the lung microenvironment and correlate with loss of lung function.

Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life: A Secondary Analysis of the Long-Term Oxygen Treatment Trial.

BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Lung Volume Reduction following Recurrent Pneumonia: An Unusual Finding in a COPD Patient.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease. Frequent pneumonias and exacerbations are known to accelerate its progression. We present a case of severe emphysema whose lung function paradoxically improved following recurrent pneumonia, without lung volume reduction surgery (LVRS). A 54-year-old female with severe COPD presented for LVRS evaluation. She was not a candidate for the surgery because of the unsuitable anatomic distribution of her emphysema. The patient experienced recurrent pneumonia over the years but her lung function and oxygen requirement showed marked improvement. Follow-up imaging studies showed decreased lung volumes and focal fibrotic changes. We believe that the improvement in her lung function overtime is the reflection of lung volume reduction as a result of parenchymal remodeling due to repeated lung infection. These findings seen in our patient contribute important information for the continued effort in developing nonsurgical lung volume reduction techniques.

Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort.

INTRODUCTION: The disease spectrum for HIV-infected individuals has shifted toward comorbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. OBJECTIVES: To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. METHODS: A cross-sectional analysis of 510 HIV-infected participants in the multicenter Lung-HIV study was performed. Data collected included demographics, biological markers of HIV, pulmonary function testing, and chest computed tomographic examinations. Emphysema and fibrosis-like changes were quantified on computed tomographic images based on threshold approaches. RESULTS: In our cohort, 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells per microliter, 39% had an HIV viral load greater than 500 copies per milliliter, and 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210; P < 0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107; P = 0.03). CONCLUSIONS: A higher HIV viral load was significantly associated with fibrosis-like changes, possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load.

Biobehavioral Prognostic Factors in Chronic Obstructive Pulmonary Disease: Results From the INSPIRE-II Trial.

OBJECTIVE: To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. METHODS: Three hundred twenty-six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life and were followed up for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. RESULTS: Sixty-nine individuals experienced a hospitalization or died over a mean follow-up period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (hazard ratio [HR] = 2.72 [95% confidence interval = 1.63-4.54], per stage); 6-minute walk (HR = 0.50 [0.34-0.73] per 500 ft), total steps (HR = 0.82 [0.71-0.94] per 1000 steps), high-sensitivity C-reactive protein (HR = 1.44 [1.01-2.06] per 4.5 mg/l), depression (HR = 1.12 [1.01-1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14-2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and 6-minute walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. CONCLUSIONS: Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD.

Factors associated with abnormal spirometry among HIV-infected individuals.

OBJECTIVE: HIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals. DESIGN: Cross-sectional cohort study. METHODS: We analyzed cross-sectional US data from the NHLBI-funded Lung-HIV consortium - a multicenter observational study of heterogeneous groups of HIV-infected participants in diverse geographic sites. Logistic regression analysis was performed to determine factors statistically significantly associated with spirometry patterns. RESULTS: A total of 908 HIV-infected individuals were included. The median age of the cohort was 50 years, 78% were men and 68% current smokers. An abnormal spirometry pattern was present in 37% of the cohort: 27% had obstructed and 10% had restricted spirometry patterns. Overall, age, smoking status and intensity, history of Pneumocystis infection, asthma diagnosis and presence of respiratory symptoms were independently associated with an abnormal spirometry pattern. Regardless of the presence of respiratory symptoms, five HIV-infected participants would need to be screened with spirometry to diagnose two individuals with any abnormal spirometry pattern. CONCLUSIONS: Nearly 40% of a diverse US cohort of HIV-infected individuals had an abnormal spirometry pattern. Specific characteristics including age, smoking status, respiratory infection history and respiratory symptoms can identify those at risk for abnormal spirometry. The high prevalence of abnormal spirometry and the poor predictive capability of respiratory symptoms to identify abnormal spirometry should prompt clinicians to consider screening spirometry in HIV-infected populations.

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

The effects of a telehealth coping skills intervention on outcomes in chronic obstructive pulmonary disease: primary results from the INSPIRE-II study.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality and reduced quality of life (QoL). Novel interventions are needed to improve outcomes in COPD patients. The present study assessed the effects of a telephone-based coping skills intervention on psychological and somatic QoL and on the combined medical end point of COPD-related hospitalizations and all-cause mortality. METHODS: We conducted a dual-site, randomized clinical trial with assessments at baseline and after 16 weeks of treatment. The study population comprised 326 outpatients with COPD aged 38 to 81 years, randomized to coping skills training (CST) or to COPD education (COPD-ED). Patients completed a battery of QoL instruments, pulmonary function tests, and functional measures and were followed up for up to 4.4 years to assess medical outcomes. RESULTS: The CST group exhibited greater improvements in psychological QoL compared with controls (p = .001), including less depression (Cohen d = 0.22 [95% confidence interval, or CI = 0.08-0.36]) and anxiety (d = 0.17 [95% CI = 0.02-0.33]), and better overall mental health (d = 0.17 [95% CI = 0.03-0.32]), emotional role functioning (d = 0.29 [95% CI = 0.10-0.48]), vitality (d = 0.27 [95% CI = 0.11, 0.42]), and social functioning (d = 0.21 [95% CI = 0.03-0.38]). A significant baseline psychological QoL by treatment group interaction revealed that CST with lower QoL at baseline achieved even greater improvements in psychological QoL compared with COPD-ED. CST participants also exhibited greater improvements in somatic QoL (p = .042), including greater improvements in pulmonary QoL (d = 0.13 [95% CI = 0.01-0.24]), less fatigue (d = 0.34 [95% CI = 0.18-0.50]), and less shortness of breath (d = 0.11 [95% CI = -0.01 to 0.23]) and greater improvement in distance walked on the Six-Minute Walk test (d = 0.09 [95% CI = 0.01-0.16]). However, there was no significant difference in risk of time to COPD-related hospitalization or all-cause mortality between CST (34 events) and COPD-ED (32 events; p = 0.430). CONCLUSIONS: A telehealth CST intervention produced clinically meaningful improvements in QoL and functional capacity, but no overall improvement in risk of COPD-related hospitalization and all-cause mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00736268.

Molecular characterization of redox mechanisms in allergic asthma.

OBJECTIVE: To investigate the molecular redox mechanisms in allergic asthma and to examine current studies of the disease to provide a basis for further investigation of oxidative stress in allergic asthma and the signaling cascades involved in its pathogenesis. DATA SOURCES: Through the use of PubMed, a broad biomedical literature review was conducted in the following areas related to the physiology and pathobiology of asthma: redox therapy, reactive oxygen species (ROS), oxidative stress, allergic asthma, and antioxidants. STUDY SELECTIONS: Studies pertaining to oxidative stress and redox signaling in the molecular pathways of inflammation and hypersensitivity in the pathogenesis of allergic asthma were reviewed. RESULTS: Allergic asthma is associated with an increase in endogenous ROS formation, leading to oxidative stress-induced damage to the respiratory system and mitigated antioxidant defenses. Exposure to environmental antigens has been shown to stimulate overproduction of ROS, resulting in abnormal physiologic function of DNA, proteins, and lipids that clinically can augment bronchial hyperresponsiveness and inflammation. Through the use of animal and human studies, oxidative stress has been determined to be important in the pathogenesis of allergic asthma. Thus, recent research suggests that the assessment of oxidative stress byproducts represents a novel method by which disease severity can be monitored. In addition, the use of redox-based therapy to attenuate levels of ROS presents a potential strategy to alleviate oxidative stress-induced airway inflammation in patients with asthma. CONCLUSION: Redox mechanisms of oxidative stress in allergic asthma appear to play a key role in the pathogenesis of the disease and represent a promising therapeutic target.

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments.

Cigarette smoking (CS) can impact the immune system and induce pulmonary disorders such as chronic obstructive pulmonary disease (COPD), which is currently the fourth leading cause of chronic morbidity and mortality worldwide. Accordingly, the most significant risk factor associated with COPD is exposure to cigarette smoke. The purpose of the present study is to provide an updated overview of the literature regarding the effect of CS on the immune system and lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the available and potential treatment options for CS-induced COPD. An extensive literature search was conducted on the PubMed/Medline databases to review current COPD treatment research, available in the English language, dating from 1976 to 2014. Studies have investigated the mechanism by which CS elicits detrimental effects on the immune system and pulmonary function through the use of human and animal subjects. A strong relationship among continued tobacco use, oxidative stress, and exacerbation of COPD symptoms is frequently observed in COPD subjects. In addition, therapeutic approaches emphasizing smoking cessation have been developed, incorporating counseling and nicotine replacement therapy. However, the inability to reverse COPD progression establishes the need for improved preventative and therapeutic strategies, such as a combination of intensive smoking cessation treatment and pharmaceutical therapy, focusing on immune homeostasis and redox balance. CS initiates a complex interplay between oxidative stress and the immune response in COPD. Therefore, multiple approaches such as smoking cessation, counseling, and pharmaceutical therapies targeting inflammation and oxidative stress are recommended for COPD treatment.

Gender Differences in Pulmonary Function, Respiratory Symptoms, and Macrophage Proteomics among HIV-Infected Smokers.

Background. HIV-infected subjects have an increased incidence of pulmonary emphysema. There are known gender differences in COPD phenotypic expression and diagnosis, but this is not well characterized in lung disease related to HIV. We analyzed a group at risk for the development of COPD (HIV-infected smokers) to determine gender differences in pulmonary symptoms, pulmonary function tests, and HRCT appearances. Methods. This was a cross-sectional, baseline analysis of a prospective study performed between 2006 and 2010. We performed symptomatic, pulmonary function, and computed tomography assessments in 243 HIV-infected smokers. In a subset bronchoalveolar lavage was performed with proteomic analysis of their alveolar macrophages. Results. The majority of the participants were male 213 (87.6%). There was significantly higher percentage of cough and phlegm production in males. There was also a lower FEV1 and a higher RV in males than females. Proteomic analysis revealed 29 proteins with at least a 2-fold higher expression in males and 13 identified proteins that were higher in females. Conclusions. In this group of HIV-infected smokers, airway symptoms and pulmonary function test abnormalities were higher in men than women. These gender differences may be due to differential expression of certain proteins in this group.

Pulmonary rehabilitation for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious lung disease affecting allogeneic hematopoietic stem cell transplantation recipients. Unfortunately, there is no standardized approach for treatment of BOS in post-hematopoietic stem cell transplantation patients. Pulmonary rehabilitation is a standard treatment in emphysema, an irreversible obstructive lung disease secondary to tobacco abuse. The National Emphysema Treatment Trial (NETT) demonstrated improved exercise tolerance, decrease dyspnea, and increase of quality of life in patients with severe emphysema after pulmonary rehabilitation. We hypothesized that pulmonary rehabilitation may benefit patients with BOS. Patients with BOS were identified retrospectively from January 2005 to the present. Patients who enrolled in pulmonary rehabilitation were included in the study. We obtained summaries via chart review of each patient's progress after pulmonary rehabilitation enrollment from his or her respective rehabilitation centers. Six-minute walk distances, spirometry, and pulmonary symptoms were compared before and after the completion of pulmonary rehabilitation. We identified 11 patients with BOS documented from their pulmonologist's clinical notes who were enrolled into pulmonary rehabilitation. Ten of the 11 patients completed pulmonary rehabilitation. All patients had improvement in their 6-minute walk distances after the completion of pulmonary rehabilitation, with an average improvement in distance of 307 feet (P value = .005). Six of the 10 patients completed Short Form-36 (SF-36) questionnaires before and after rehabilitation. There was a significant improvement in the physical functioning score (P value = 0.029). Pulmonary rehabilitation seems to improve 6-minute walk distance, subjective symptoms of dyspnea, and exercise tolerance in patients with BOS. This may be an important adjunctive therapy for a debilitating disease with limited treatment options.

HIV and asthma, is there an association?

OBJECTIVE: To evaluate whether asthma and airway hyper-responsiveness are associated with HIV infection. METHODS: We reviewed the literature on HIV-associated pulmonary diseases, pulmonary symptoms, and immune changes which may play a role in asthma. The information was analyzed comparing the pre-HAART era to the post-HAART era data. RESULTS: HIV-seropositive individuals commonly experience respiratory complaints yet it is unclear if the frequency of these complaints have changed with the initiation of HAART. Changes in pulmonary function testing and serum IgE are seen with HIV infection even in the post-HAART era. An increased prevalence of asthma among HIV-seropositive children treated with HAART has been reported. CONCLUSION: The spectrum of HIV-associated pulmonary disease has changed with the introduction of HAART. Current data is limited to determine if asthma and airway hyper-responsiveness are more common among HIV-seropositive individuals treated with HAART.

Effects of humor and laughter on psychological functioning, quality of life, health status, and pulmonary functioning among patients with chronic obstructive pulmonary disease: a preliminary investigation.

OBJECTIVE: Previous research indicates the beneficial effects of humor among healthy adults. Little is known about the physical and psychological effects of sense of humor and laughter among patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD (n = 46; mean age ± SD, 66.9 ± 9.9 years) completed assessments of sense of humor, depression, anxiety, quality of life, and recent illness. A subset of patients (n = 22) completed a laughter induction study and were randomly assigned to view either a humorous or a neutral video. Pulmonary function, mood state, and dyspnea were assessed before and after the video. RESULTS: Sense of humor was associated with fewer symptoms of depression and anxiety and an enhanced quality of life. However, the induction of laughter led to lung hyperinflation. CONCLUSION: Sense of humor among patients with COPD is associated with positive psychological functioning and enhanced quality of life, but laughing aloud may cause acute deterioration in pulmonary function secondary to worsened hyperinflation.

HIV-associated lung infections and complications in the era of combination antiretroviral therapy.

The spectrum of lung diseases associated with HIV is broad, and many infectious and noninfectious complications of HIV infection have been recognized. The nature and prevalence of lung complications have not been fully characterized since the Pulmonary Complications of HIV Infection Study more than 15 years ago, before antiretroviral therapy (ART) increased life expectancy. Our understanding of the global epidemiology of these diseases in the current ART era is limited, and the mechanisms for the increases in the noninfectious conditions, in particular, are not well understood. The Longitudinal Studies of HIV-Associated Lung Infections and Complications (Lung HIV) Study (ClinicalTrials.gov number NCT00933595) is a collaborative multi-R01 consortium of research projects established by the National Heart, Lung, and Blood Institute to examine a diverse range of infectious and noninfectious pulmonary diseases in HIV-infected persons. This article reviews our current state of knowledge of the impact of HIV on lung health and the development of pulmonary diseases, and highlights ongoing research within the Lung HIV Study.

Religious and spiritual coping and quality of life among patients with emphysema in the National Emphysema Treatment Trial.

BACKGROUND: Although prior research indicates that religious and spiritual coping is associated with positive health outcomes, few studies have examined religious and spiritual coping among patients with emphysema. OBJECTIVE: To describe the utilization of religious and spiritual coping and its relationship to quality of life among patients with emphysema, in a 2-year longitudinal follow-up study. METHODS: Forty patients with emphysema (mean age 63.5 ± 6.0 y, 8 women) who participated in the National Emphysema Treatment Trial were matched on age, sex, race, and education with 40 healthy individuals recruited from the community. We conducted baseline assessment of overall coping strategies, psychological functioning, quality of life, pulmonary function, and exercise capacity, and we assessed overall coping strategies and religious and spiritual coping at 2-year follow-up. RESULTS: Ninety percent of the patients with emphysema considered themselves at least slightly religious and spiritual. The patients reported using both negative religious coping (eg, questioning God) and positive religious coping (eg, prayer) more than the healthy control subjects at follow-up. However, greater use of religious and spiritual coping was associated with poorer illness-related quality of life. CONCLUSIONS: Patients with emphysema appear to use various coping strategies in responding to their illness. Future research should investigate if patients using religious and spiritual coping would benefit from interventions to address emotional distress and reduced quality of life.

Tobacco use and cessation among women: research and treatment-related issues.

The prevalence of tobacco use in women has increased over the past century. This has resulted in dramatic increases in smoking-related lung diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. There is growing literature suggesting that women may be more susceptible than men to the effects of tobacco and to the development of COPD. Women may also have specific barriers that interfere with smoking cessation. This article addresses possible differences in lung function decline and nicotine metabolism in women compared to men. Differences in COPD between the sexes are discussed. Finally, barriers to smoking cessation in women are presented.