Akshay Sood

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. METHODS We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. RESULTS Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONS Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.).

An official American thoracic society workshop report: obesity and asthma.

RATIONALE The developed world is currently facing an epidemic of obesity. With the increased prevalence of obesity has come the recognition that obesity is a risk factor for asthma. OBJECTIVES The purpose of this workshop was to bring together experts in the field of asthma, with experts in the field of obesity to review the current state-of-the-art knowledge regarding obesity and asthma, with the goal of furthering our understanding of the link between these two disease entities to help define important future directions for research. METHODS Speakers were invited to give presentations highlighting recent developments in their area of expertise that were related to obesity and lung disease. These presentations were followed by interactive discussion. A writing committee from among the participants produced a document summarizing the proceedings. MEASUREMENTS AND MAIN RESULTS The participants found that obesity was a risk factor for asthma in all demographic groups studied. Asthma in the obese may represent a unique phenotype of asthma, with more severe disease that does not respond as well to conventional therapy. Factors that could contribute to the pathogenesis of asthma in the obese include both mechanical factors and altered inflammation and immune responses related to the obese state. CONCLUSIONS There is an urgent need for research to better understand the mechanisms of asthma in the obese, and to develop new therapies specifically targeted to this unique patient population.

Association between asthma and serum adiponectin concentration in women.

Background: The association of murine asthma with adiposity may be mediated by adiponectin, an anti-inflammatory adipokine with reduced serum concentrations in obese subjects. A study was undertaken to examine whether the serum adiponectin concentration is associated with human asthma and whether it explains the association between adiposity and asthma, particularly in women and in premenopausal women. Methods: A cross-sectional analysis was performed of 2890 eligible subjects at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and its YALTA ancillary study who had either current asthma or never asthma at that evaluation. Obesity was defined as body mass index (BMI) ⩾30 kg/m2. Multivariable logistic regression analysis was performed with current asthma status as the dependent variable. Results: Women, but not men, with current asthma had a lower mean unadjusted serum adiponectin concentration than those with never asthma (p<0.001; p for sex interaction <0.001). Similarly, current asthma was related to obesity only in women (OR 3.31, 95% CI 2.00 to 5.46, p for sex interaction = 0.004); this association was little affected by adjusting for serum adiponectin. The prevalence of current asthma in premenopausal women was reduced in the highest compared with the lowest tertile of serum adiponectin concentration (OR 0.46, 95% CI 0.26 to 0.84, p = 0.03), after adjusting for BMI. However, the interaction between serum adiponectin concentration and BMI category on current asthma status was not significant in premenopausal women or women overall. Conclusions: A high serum adiponectin concentration may protect against current asthma in premenopausal women but does not explain the association between asthma and adiposity.

Leptin, adiponectin and pulmonary diseases.

Adipose tissue produces leptin and adiponectin - energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine studies. Leptin and adiponectin and their respective receptors are expressed in the human lung. The association between systemic or airway leptin and asthma in humans is currently controversial, particularly among adults. The majority of the evidence among children however suggests that systemic leptin may be associated with greater asthma prevalence and severity, particularly among prepubertal boys and peripubertal/postpubertal girls. Systemic and airway leptin concentrations may also be disproportionately higher in chronic obstructive pulmonary disease (COPD) patients, particularly among women, and reflect greater airway inflammation and disease severity. Quite like leptin, the association between systemic and airway adiponectin and asthma in humans is also controversial. Some but not all studies, demonstrate that serum adiponectin concentrations are protective against asthma among premenopausal women and peripubertal girls. On the other hand, serum adiponectin concentrations are inversely associated with asthma severity among boys but positively associated among men. Further, systemic and airway adiponectin concentrations are higher in COPD patients than controls, as demonstrated by case-control studies of men. Systemic adiponectin is also positively associated with lung function in healthy adults but inversely associated with lung function in subjects with COPD. It is therefore possible that pro-inflammatory effects of adiponectin dominate under certain physiologic conditions and anti-inflammatory effects under others. The adipokine-lung disease literature has critical gaps that include a lack of adequately powered longitudinal or weight-intervention studies; inadequate adjustment for confounding effect of obesity; and unclear understanding of potential sex interactions. It is also uncertain whether adipokine derangements precede pulmonary disease or are a consequence of it. Future research will determine whether modulation of adipokines, independent of BMI, may allow novel ways to prevent or treat inflammatory pulmonary conditions.

Altered Resting and Exercise Respiratory Physiology in Obesity

Obesity, particularly severe obesity, affects resting and exercise-related respiratory physiology. Severe obesity classically produces a restrictive ventilatory abnormality characterized by reduced expiratory reserve volume. Obstructive ventilatory abnormality may also be associated with abdominal obesity. Decreased peak work rates are usually seen among obese subjects in a setting of normal or decreased ventilatory reserve and normal cardiovascular response to exercise. Weight loss may reverse many adverse physiologic consequences of severe obesity on the respiratory system.

Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace.

Hypersensitivity pneumonitis-like granulomatous lung disease with nontuberculous mycobacteria from exposure to hot water aerosols.

Objective Human activities associated with aerosol-generating hot water sources are increasingly popular. Recently, a hypersensitivity pneumonitis (HP)-like granulomatous lung disease, with non-tuberculous mycobacteria from exposure to hot water aerosols from hot tubs/spas, showers, and indoor swimming pools, has been described in immunocompetent individuals (also called “hot tub lung”). Our objective in this study was to examine four additional cases of hot tub lung and compare these cases with others reported in the English print literature on this disease. Data sources and extraction We retrospectively reviewed all cases (n = 4) of presumptively diagnosed hot tub lung in immunocompetent individuals at the various physician practices in Springfield, Illinois, during 2001–2005. In addition, we searched MEDLINE for cases of hot tub lung described in the literature. Data synthesis We summarized the clinical presentation and investigations of four presumptive cases and reviewed previously reported cases of hot tub lung. Conclusions There is a debate in the literature whether hot tub lung is an HP or a direct infection of the lung by nontuberculous mycobacteria. Primary prevention of this disease relies on ventilation and good use practices. Secondary prevention of this disease requires education of both the general public and clinicians to allow for the early diagnosis of this disease.

Intakes of long-chain omega-3 (n-3) PUFAs and fish in relation to incidence of asthma among American young adults: the CARDIA study.

BACKGROUND Although long-chain ω-3 (n-3) PUFAs (LCω3PUFAs) have been linked to the prevention of some inflammatory disorders, little is known about the association between these fatty acids and incidence of asthma. OBJECTIVE The objective was to prospectively investigate the association between LCω3PUFAs and fish intake and incidence of asthma among American young adults. DESIGN A 20-y follow-up longitudinal analysis was conducted in a biracial cohort of 4162 Americans, aged 18-30 y, with a history of asthma at baseline in 1985. Diet was assessed by a validated interviewer-administered quantitative food-frequency questionnaire at the examinations in 1985, 1992, and 2005. Incident self-reported asthma was defined as having a physician diagnosis of asthma and/or the use of asthma medications between 1985 and 2005. RESULTS During the 20-y follow-up, 446 incident cases of asthma were identified. LCω3PUFA intake was significantly inversely associated with incidence of asthma after adjustment for sociodemographic, major lifestyle, and dietary confounders. The multivariable-adjusted HR for the highest quintile of LCω3PUFA intake as compared with the lowest quintile was 0.46 (95% CI: 0.33, 0.64; P-trend < 0.01). However, a higher frequency of nonfried fish consumption was not significantly associated with the risk of asthma. DHA showed a greater inverse association than did EPA. The association between LCω3PUFAs and incident asthma was not appreciably modified by sex, race, BMI, smoking status, or atopic status. CONCLUSION This study showed that intakes of LCω3PUFAs are inversely longitudinally associated with the incidence of asthma in American young adults.

Indoor fuel exposure and the lung in both developing and developed countries: An update

Almost 3 billion people worldwide burn solid fuels indoors. Despite the large population at risk worldwide, the effect of exposure to indoor solid fuel smoke has not been adequately studied. Indoor air pollution from solid fuel use is strongly associated with chronic obstructive pulmonary disease, acute respiratory tract infections, and lung cancer, and weakly associated with asthma, tuberculosis, and interstitial lung disease. Tobacco use further potentiates the development of respiratory disease among subjects exposed to solid fuel smoke. There is a need to perform additional interventional studies in this field.

Low serum adiponectin predicts future risk for asthma in women

RATIONALE Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women. OBJECTIVES To determine longitudinal association between serum adiponectin and incident asthma among women. METHODS We used data from examinations at Years 10, 15, and 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. In our primary analysis, the association of CARDIA Year 15 serum adiponectin concentration with Year 20 incident asthma was evaluated. In our secondary analysis, the converse direction, that is, the association of CARDIA Year 10 prevalent asthma with Year 15 serum adiponectin, was evaluated, using logistic regression techniques. MEASUREMENTS AND MAIN RESULTS Our primary analysis included 1,450 women, mostly premenopausal. Multivariable analyses demonstrated that the lowest tertile of Year 15 serum adiponectin concentration (<7 mg/L) predicted significantly higher risk for incident asthma at Year 20 among women (odds ratio, 2.07; 95% confidence interval, 1.05, 4.10), and particularly among current smokers (interaction P = 0.051). Further, low serum adiponectin was more important than body mass index in predicting the risk for incident asthma among women. We also showed that the converse relationship was not true; that is, Year 10 prevalent asthma did not predict Year 15 serum adiponectin concentrations in women. CONCLUSIONS Serum adiponectin affects future risk for asthma in women and not vice versa. Measures that raise systemic adiponectin concentrations may lead to newer ways to prevent asthma among women, particularly among those who smoke.