Background: Matrix metalloproteinases (MMPs) are involved in the remodelling and degradation of extracellular matrix and may play a role in pulmonary tissue destruction in cystic fibrosis (CF). Methods: Bronchoalveolar lavage (BAL) fluid levels of MMP-8, MMP-9, and their natural inhibitor TIMP-1 were measured on two occasions within 18 months in 23 children with mild CF, 13 of whom were treated with DNase. Results: MMP-8 (39.3 (6.8) v 0.12 (0.01) ng/ml), MMP-9 (58.0 (11.4) v 0.5 (0.02) ng/ml), and the molar ratio of MMP-9/TIMP-1 (0.36 (0.05) v 0.048 (0.01)) were significantly higher in patients with CF than in control children without lung disease. Gelatine zymography showed the typical banding pattern of neutrophil derived MMP-9, including 130 kDa NGAL-MMP-9 complex and 92 kDa latent MMP-9 bands; 85 kDa bands (corresponding to active MMP-9) were seen in all patients. There was a close correlation between BAL fluid concentrations of MMPs and α 2 -macroglobulin, a marker of alveolocapillary leakage. After 18 months MMP levels were increased in untreated patients and decreased in patients treated with DNase. Conclusions: Uninhibited MMPs may contribute to pulmonary tissue destruction even in CF patients with mild lung disease that may be positively affected by treatment with DNase.

The obligate intracellular pathogen Chlamydia pneumoniae is associated with chronic respiratory, atherosclerotic, and rheumatic disease. The alveolar macrophage (AM) is a potential target cell for the pathogen and may contribute to respiratory immunopathology. We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C. pneumoniae and AM from 12 healthy volunteers. Inflammatory responses were evaluated through lucigenin-amplified chemiluminescence; secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin 8 (IL-8); and expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen-DR (HLA-DR). C. pneumoniae readily induced productive infection in the AM. Inclusions containing replicating pathogens could be maintained for up to 120 h. Morphologically similar infection patterns were seen ex vivo in AM collected from six patients with known C. pneumoniae pneumonia. AM responded to the infection with a marked, dose-dependent release of reactive oxygen species, TNF-alpha, IL-1beta, and IL-8. ICAM-1 expression remained unchanged, but HLA-DR was significantly upregulated. Our data indicate that the release of antimicrobial mediators cannot prevent chlamydial infection and replication in AM, but may be involved in amplification of the local inflammatory response in C. pneumoniae pneumonia.

Background-Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN) , interleukin (IL)-2, tumour necrosis factor (TNF) , IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry. Methods-Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease. Results-Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant diVerences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells. Conclusions-Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood. (Thorax 2001;56:487-493)

Background COVID-19, the pandemic caused by the severe acute respiratory syndrome coronavirus-2, is challenging healthcare systems worldwide. Little is known about problems faced by emergency medical services—particularly helicopter services—caring for suspected or confirmed COVID-19 patients. We aimed to describe the issues faced by air ambulance services in Europe as they transport potential COVID-19 patients. Methods Nine different HEMS providers in seven different countries across Europe were invited to share their experiences and to report their data regarding the care, transport, and safety measures in suspected or confirmed COVID-19 missions. Six air ambulance providers in six countries agreed and reported their data regarding development of special procedures and safety instructions in preparation for the COVID-19 pandemic. Four providers agreed to provide mission related data. Three hundred eighty-five COVID-19-related missions were analysed, including 119 primary transport missions and 266 interfacility transport missions. Results All providers had developed special procedures and safety instructions in preparation for COVID-19. Ground transport was the preferred mode of transport in primary missions, whereas air transport was preferred for interfacility transport. In some countries the transport of COVID-19 patients by regular air ambulance services was avoided. Patients in interfacility transport missions had a significantly higher median (range) NACA Score 4 (2-5) compared with 3 (1-7), needed significantly more medical interventions, were significantly younger (59.6 ± 16 vs 65 ± 21 years), and were significantly more often male (73% vs 60.5%). Conclusions All participating air ambulance providers were prepared for COVID-19. Safe care and transport of suspected or confirmed COVID-19 patients is achievable. Most patients on primary missions were transported by ground. These patients were less sick than interfacility transport patients, for whom air transport was the preferred method.

Background: Pulmonary inflammation in bronchiectasis, pneumonia and idiopathic pulmonary fibrosis (IPF) is dominated by neutrophils. Pathophysiologic differences are seen in the degree of airway and tissue destruction. Neutrophil activation and neutrophil proteolytic activity might differ between bronchiectasis, pneumonia and IPF. Objective: The aim of this study was to determine whether levels of inflammatory and protective markers in bronchoalveolar lavage (BAL) differed among cases of bronchiectasis, pneumonia and IPF. Methods: We studied 11 bronchiectasis patients (group 1), 30 pneumonia patients (group 2), 15 IPF patients (group 3) and 12 healthy volunteers (group 4). In the bronchoalveolar lavage fluid, concentrations of α₁-proteinase inhibitor, myeloperoxidase (MPO) and elastase-α₁PI complex were determined using immunoluminometric assays. Elastase inhibition capacity (EIC) and elastase activity were determined using a colorimetric assay. Results: No EIC, but free elastase activity, was found in 82% of group 1, 20% of group 2, 20% of group 3 and 0% of group 4. Median MPO concentration was highest in group 1: 7,951 ng/ml (16th–84th percentile [16–84%]: 256–36,342) vs. 692 ng/ml (106–2,279; group 2), 332 ng/ml (98–1,657; group 3), and 0.12 ng/ml (0.08–0.26; group 4). Bronchiectasis patients with bronchial Pseudomonas infection showed higher amounts of neutrophils (p < 0.01) and higher elastase activity (p < 0.05) than patients with sterile lavage. Conclusion: Bronchiectasis patients show a severe imbalance between neutrophil activity and protective molecules leading to possible lung destruction. Chronic Pseudomonas infection might trigger neutrophil activation. Future research and treatment strategies should focus on increased bacterial clearance and inhibition of neutrophil toxicity.