The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1

<p>Abstract</p> <p>Background</p> <p>Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time.</p> <p>Methods</p> <p>Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis.</p> <p>Results</p> <p>We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed.</p> <p>Conclusions</p> <p>Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.</p

Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease

BACKGROUND: Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction. Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies. METHODS: Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD. Participants were recruited from all 48 contiguous U.S. states by random digit dialing. Lifetime ETS exposure was ascertained by structured telephone interview. We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD. RESULTS: Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD. The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21). The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84). The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure. CONCLUSION: ETS exposure may be an important cause of COPD. Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure

The incidence of interstitial lung disease 1995–2005: a Danish nationwide population-based study

<p>Abstract</p> <p>Background</p> <p>Current data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005.</p> <p>Methods</p> <p>All persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories.</p> <p>Results</p> <p>A total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82–28.46) per 100,000 person-years to 19.36 (95% CI 18.26–20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84–35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere".</p> <p>Conclusion</p> <p>The incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases.</p

Ethnic differences in smoking intensity and COPD risk: an observational study in primary care

A.G. was in receipt of an NIHR In-Practice Fellowship while completing this work. S.H. and R.M. were supported by a Curriers’ Company Millennium Healthcare Bursary. P.S. was supported by a UK Medical Research Council fellowshi

Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients

Purpose: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. Methods: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent 18F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of 18F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). Results: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). Conclusion: IPF patients have increased pulmonary uptake of 18F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring. © 2013 The Author(s)

Is there a uniform approach to the management of diffuse parenchymal lung disease (DPLD) in the UK? A national benchmarking exercise

BACKGROUND: Benchmarking is the comparison of a process to the work or results of others. We conducted a national benchmarking exercise to determine how UK pulmonologists manage common clinical scenarios in diffuse parenchymal lung disease (DPLD), and to determine current use and availability of investigative resources. We compared management decisions to existing international guidelines. METHODS: Consultant members of the British Thoracic Society were mailed a questionnaire seeking their views on the management of three common scenarios in DPLD. They were asked to choose from various management options for each case. Information was also obtained from the respondents on time served as a consultant, type of institution in which they worked and the availability of a local radiologist and histopathologist with an interest/expertise in thoracic medicine. RESULTS: 370 out of 689 consultants replied (54% response rate). There were many differences in the approach to the management of all three cases. Given a scenario of relapsing pulmonary sarcoidosis in a lady with multiple co-morbidities, half of respondents would institute treatment with a variety of immunosuppressants while a half would simply observe. 42% would refer a 57-year old lady with new onset DPLD for a surgical lung biopsy, while a similar number would not. 80% would have referred her for transplantation, but a fifth would not. 50% of consultants from district general hospitals would have opted for a surgical biopsy compared to 24% from cardiothoracic centres: this may reflect greater availability of a radiologist with special interest in thoracic imaging in cardiothoracic centres, obviating the need for tissue diagnosis. Faced with an elderly male with high resolution CT thorax (HRCT) evidence of usual interstitial pneumonia (UIP), three quarters would observe, while a quarter would start immunosuppressants. 11% would refer for a surgical biopsy. 14% of UK pulmonologists responding to the survey revealed they had no access to a radiologist with an interest in thoracic radiology. CONCLUSION: From our survey, it appears there is a lack of consensus in the management of DPLD. This may reflect lack of evidence, lack of resources or a failure to implement current guidelines