Prognostic Significance of Cavitary Lung Nodules in Granulomatosis With Polyangiitis (Wegener's): A Clinical Imaging Study of 225 Patients.

OBJECTIVE: Granulomatosis with polyangiitis (Wegener's) (GPA) is a systemic necrotizing vasculitis in which pulmonary nodules are a common manifestation. Our study examined whether pulmonary nodules, and nodule type (solid versus cavitary), are associated with different disease manifestations and outcomes. METHODS: Demographic, clinical, biologic, and radiologic data at diagnosis and during followup and treatments of GPA patients followed at the Mount Sinai Hospital (Canada) Vasculitis Clinic were analyzed. Patients were separated by the absence of lung nodules, presence of solid nodules only, and presence of cavitary nodules (+/- solid nodules). The study outcomes included followup lung imaging, relapses, and deaths. RESULTS: Of 225 patients with GPA, 46 had solid nodules only and 44 had cavitary nodules at diagnosis. Demographic and clinical manifestations were similar in the patient subgroups at diagnosis. Cyclophosphamide (CYC) was used for induction after diagnosis in 76.7% of patients with cavitary nodules, compared with 64.7% of patients without nodules and 51.1% of patients with solid nodules (P = 0.04). The mean ± SD followup after diagnosis was 106.6 ± 92.6 months, and 6 of the patients died. In multivariable analysis, diagnosis before 2000 or pulmonary nodule cavitation at diagnosis were associated with relapse, with a hazard ratio of 0.38 (95% confidence interval [95% CI] 0.22-0.65; P < 0.001) and 1.53 (95% CI 1.00-2.33; P = 0.05), respectively, after adjustment for CYC use. CONCLUSION: The presence of cavitary nodules led to increased use of CYC but had no impact on survival. Relapse occurred more often, however, in patients with cavitary nodules than in those with solid nodules or no nodules, and should be studied in other cohorts.

Hemosiderin in sputum macrophages may predict infective exacerbations of chronic obstructive pulmonary disease: a retrospective observational study.

BACKGROUND: Infective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum. Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation. Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD. The purpose of our study was to determine if hemosiderin in sputum macrophages is related to infective exacerbations of COPD. METHODS: We undertook a retrospective observational study of 54 consecutive patients who presented with an exacerbation of COPD and had sputum examined including assessment for hemosiderin in alveolar macrophages. The relation between infective exacerbations in the previous two years and the percent of hemosiderin-positive macrophages was analyzed with linear regression. To account for the non-parametric distribution of infective exacerbations, negative binomial regression modelling was used to account for other covariates. RESULTS: The percent of hemosiderin positive alveolar macrophages (hemosiderin index), analyzed parametrically and non-parametrically, demonstrated a significant correlation with increasing numbers of infective exacerbations in the previous two years. In a multivariate regression analysis, hemosiderin index was an independent predictor of infective exacerbations. COPD patients with raised hemosiderin index (≥20%) had higher levels of sputum IL-6 compared to patients with lower levels (<20%). CONCLUSIONS: High hemosiderin index in sputum alveolar macrophages measured at the time of AECOPD may be related to the frequency of infective exacerbations of COPD.

Differences in hyperpolarized (3) He ventilation imaging after 4 years in adults with cystic fibrosis.

PURPOSE: To evaluate cystic fibrosis (CF) subjects over 4 years using (3) He magnetic resonance imaging (MRI), pulmonary function tests, and track hospitalization and physician visits. MATERIALS AND METHODS: Five CF adults provided written informed consent to an approved protocol and underwent MRI, spirometry, and plethysmography at baseline, 7 days, and 4 ± 1 years later. (3) He MRI ventilation defect percent (VDP) was generated for all subjects and timepoints. RESULTS: After 4 years, mean forced expiratory volume in 1 second / forced vital capacity (FEV1 /FVC) was lower (P = 0.01) in all subjects and there were no other pulmonary function test changes. Two CF adults showed significantly elevated (worse) (3) He VDP at baseline and after 4 years they had significantly greater (worsened) VDP (P = 0.02), without a significant FEV1 decline (P = 0.06) but with a greater number of exacerbations (P < 0.05). Baseline VDP strongly correlated with FEV1 (r(2) = 0.98, P = 0.0007) at 4-year follow-up. CONCLUSION: For two CF subjects, VDP was significantly worse at baseline and worsened over 4 years, which was in agreement with a greater number of hospitalizations and clinic visits. These results are limited by the very small sample size, but the strong VDP correlation with longitudinal changes in FEV1 generates the hypothesis that abnormal VDP may temporally precede FEV1 decline in CF subjects; this must be tested in a larger CF study.