Nadia N. Hansel

BACKGROUND: Recent worldwide reports of community-onset skin abscesses, outbreaks of furunculosis, and severe pneumonia associated with methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosome mec (SCCmec) type IV indicate that MRSA infections are evolving into a community-related problem. The majority of cases reported to date involve skin and soft-tissue infections, with severe pneumonia representing a relatively rare phenomenon. During a 2-month period in the winter of 2003-2004, four healthy adults presented to 1 of 2 Baltimore hospitals with severe necrotizing MRSA pneumonia in the absence of typical risk factors for MRSA infection. METHODS: Patients' MRSA isolates were characterized by strain typing with use of pulsed-field gel electrophoresis and SCCmec typing with use of a multiplex polymerase chain reaction (PCR) assay and detection of PVL genes by PCR. RESULTS: All 4 patients' MRSA isolates carried the PVL genes and the SCCmec type IV element and belonged to the USA300 pulsed-field type. These 3 findings are among the typical characteristics of community-onset MRSA strains. In addition, 2 of our patients had concomitant influenza A diagnosed, which likely contributed to the severity of their presentation. CONCLUSIONS: To our knowledge, these patients represent the first reported North American adults with severe community-onset MRSA pneumonia caused by strains carrying the PVL genes.

BACKGROUND: Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms. METHODS: We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest. RESULTS: Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27±0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used bronchodilators and 23% used inhaled glucocorticoids. CONCLUSIONS: Although they do not meet the current criteria for COPD, symptomatic current or former smokers with preserved pulmonary function have exacerbations, activity limitation, and evidence of airway disease. They currently use a range of respiratory medications without any evidence base. (Funded by the National Heart, Lung, and Blood Institute and the Foundation for the National Institutes of Health; SPIROMICS ClinicalTrials.gov number, NCT01969344.).

the development of curative and regenerative therapies that go beyond the largely symptomatic treatment options available; and (6) deployment of public health preventive strategies for banning smoking and maintaining clean air. We are fully cognisant that the scientific evidence to support some of our proposals is lacking. However, it is the intention of the Commission to generate discourse and debate, catalyse momentum, and provide a much-needed new vision to set the course towards the elimination of COPD.

BACKGROUND: The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. METHODS: We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. RESULTS: 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p=0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p=0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p<0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p<0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. CONCLUSION: Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00608764.