Jesper Rømhild Davidsen

Neutrophil and (alveolar) macrophage immunity is considered crucial for eliminating Aspergillus fumigatus. Data derived from bronchoalveloar lavage (BAL) characterizing the human immuno-pulmonary response to Aspergillus fumigatus are non-existent. To obtain a comprehensive picture of the immune pathways involved in chronic pulmonary aspergillosis (CPA), we performed proteome analysis on AL of 9 CPA patients and 17 patients with interstitial lung disease (ILD). The dihydrorhodamine (DHR) test was also performed on BAL and blood neutrophils from CPA patients and compared to blood neutrophils from healthy controls (HCs). BAL from CPA patients primarily contained neutrophils, while ILD BAL was also characterized by a large fraction of lymphocytes; these differences likely reflecting the different immunological etiologies underlying the two disorders. BAL and blood neutrophils from CPA patients displayed the same oxidative burst capacity as HC blood neutrophils. Hence, immune evasion by Aspergillus involves other mechanisms than impaired neutrophil oxidative burst capacity per se. CPA BAL was enriched by proteins associated with innate immunity, as well as, more specifically, with neutrophil degranulation, Toll-like receptor 4 signaling, and neutrophil-mediated iron chelation. Our data provide the first comprehensive target organ-derived immune data on the human pulmonary immune response to Aspergillus fumigatus.

Summary Objective The Objective was to determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. Methods Individuals with RA visiting Rheumatological outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnoea, cough, recurrent pneumonia, prior severe pneumonia or a chest X‐ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high‐resolution CT (HRCT) <12 months or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if ≥10 B‐lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV). An ILD‐specialised thoracic radiologist assessed HRCT, followed by a multi‐disciplinary team discussion, which was the reference standard. The accepted window of HRCT was <30 days after TUS was performed. Results 77 participants received HRCT <30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% CI: 61.2% to 95.0%) and a specificity of 51.9% (95% CI: 37.8% to 65.7%), corresponding to a PPV of 42.2% (95%CI 27.7% to 57.8%) and an NPV of 87.5% (95% CI 71.0% to 96.5%). Conclusion To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA. image