Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias.

BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

Antigen avoidance and environmental inhalation challenge for successful diagnosis of fibrotic hypersensitivity pneumonitis mimicking idiopathic pulmonary fibrosis.

A 77-year-old man was initially diagnosed with idiopathic pulmonary fibrosis (IPF) and treated with anti-fibrotic nintedanib. Despite undergoing anti-fibrotic treatment for one year, his condition remained unstable. The patient was admitted to our hospital for exertional dyspnea. We performed an exposure assessment, including 2-week antigen avoidance and an environmental inhalation challenge, and successfully re-diagnosed him with fibrotic hypersensitivity pneumonitis (HP), known as chronic farmer's lung. Adding oral glucocorticoids to the nintedanib treatment improved his condition. Although antigen avoidance and environmental inhalation challenge tests are not standardized, they may be useful for diagnosing fibrotic HP when properly applied.

Macrolide resistant Mycobacterium avium complex pulmonary disease following clarithromycin and ethambutol combination therapy.

RATIONALE: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear. OBJECTIVE: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease. METHODS: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test. RESULTS: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593). CONCLUSIONS: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

[Clinical analysis of idiopathic nonspecific interstitial pneumonia with unfavorable outcome].

Nonspecific interstital pneumonia (NSIP) is associated with an excellent response to steroidal therapy. However, it was reported that some cases of NSIP might have an unfavorable outcome in spite of aggressive therapy. In this study, we explored the prognosis for 23 patients with NSIP and examined matched groups of 18 patients with treatment-responsive or naturally recovered idiopathic NSIP, and 5 patients with idiopathic NSIP who fared poorly despite therapy. The patients who had poor prognoses were, significantly, all non-smoking women. Histologic examination revealed that the cases with progressive, idiopathic NSIP were in all cases of the fibrotic type. By contrast, only 39% of those with a good prognosis, were fibrotic. No significant differences in CT appearance were noted between the two cohorts. These findings provide a potential clinical marker of therapy outcome of in idiopathic NSIP.

Clinical characteristics and prognosis of chronic pulmonary aspergillosis.

BACKGROUND: The details of the clinical characteristics of patients with chronic pulmonary aspergillosis (CPA) have not been fully understood. METHOD: One hundred twenty-nine consecutive patients with isolation of Aspergillus species by culture from respiratory specimens who attended our hospital between October 2001 and September 2009 were enrolled. Patients diagnosed with chronic pulmonary aspergillosis (CPA) were retrospectively reviewed for clinical characteristics and prognosis, compared with patients with Aspergillus species colonization. RESULTS: Forty-two (32.6%) were diagnosed with CPA, whereas 87 (67.4%) with colonization. Aspergillus fumigatus was significantly more frequently detected in the CPA group than in the colonization group. Regarding underlying diseases, CPA patients had a significantly higher prevalence of a history of pulmonary tuberculosis and diabetes mellitus than colonization patients. There were no significant differences between the CPA and colonization group in Aspergillus antigen titers. Positivity for Aspergillus precipitating antibody was 74.3% in CPA and 15.8% in colonization, respectively. Sensitivity and specificity of Aspergillus precipitating antibody for the determination of CPA was 74.4% and 84.1%, respectively.Patients with CPA had significantly shorter survival than patients with colonization (mortality rate 50.0% vs. 13.8%, observation periods: 28.7 ± 26.6 months) (p < 0.0001). Multivariable analysis revealed that BMI was an independent predictor of prognosis (Odds Ratio, 1.973; p = 0.0223). CONCLUSIONS: CPA is a disease with a poor prognosis, which shows distinct clinical characteristics from colonization.