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DLCO was below the lower limit of normal in 24% of participants. Ground-glass opacities (GGO) with &gt;10% distribution in at least one of four pulmonary zones were present in 25% of participants, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted OR 4.2, 95% CI 1.1-15.6) and lower performance in usual activities.3 months after admission for COVID-19, one-fourth of the participants had chest CT opacities and reduced diffusing capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function.<br />After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking.<br />In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT).<br />Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time.<br />A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities &gt;100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.<br />100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.Positive results in preclinical studies of the triple combination of elexacaftor, tezacaftor and ivacaftor, performed in airway epithelial cell cultures obtained from patients harboring F508del-CFTR, translated to impressive clinical outcomes for subjects carrying this mutation in clinical trials and approval of TRIKAFTATM Encouraged by this correlation, we were prompted to evaluate the effect of the elexacaftor, tezacaftor and ivacaftor triple combination on primary nasal epithelial cultures obtained from individuals with rare Class II cystic fibrosis causing mutations; G85E, M1101K and N1303K for which TRIKAFTATM is not approved. Cultures from individuals homozygous for M1101K responded better than cultures harboring G85E and N1303K after treatment with the triple combination with respect to improvement in regulated channel function and protein processing. A similar genotype specific effect of the triple combination was observed when the different mutations were expressed in HEK-293 cells, supporting the hypothesis that these modulators may act directly on the mutant proteins. Detailed studies in nasal cultures and HEK-293 cells showed that the corrector elexacaftor, exhibited dual activity as both corrector and potentiator and suggested that the potentiator activity contributes to its pharmacological activity. These preclinical studies using nasal epithelial cultures identified mutation genotypes for which elexacaftor, tezacaftor and ivacaftor may produce clinical responses that are comparable to, or inferior to those observed for F508del-CFTR.Cystic fibrosis is a life-shortening, multiorgan, autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most prominent clinical manifestation in CF is the development of progressive lung disease characterised by an intense, chronic inflammatory airway response that culminates in respiratory failure, and ultimately death. In recent years, a new class of therapeutics which have the potential to correct the underlying defect in CF, known as CFTR modulators, have revolutionised the field. Despite the exciting success of these drugs, their impact on airway inflammation, and its long-term consequences, remain undetermined. In addition, studies querying the absolute requirement for infection as a driver of CF inflammation have challenged the traditional consensus on CF pathogenesis, and also emphasise the need to prioritise complementary anti-inflammatory treatments in CF. Macrophages, often overlooked in CF research despite their integral role in other chronic inflammatory pathologies, have increasingly become recognised as key players in the initiation, perpetuation, and resolution of CF lung inflammation, perhaps as a direct result of CFTR dysfunction. These findings suggest that macrophages may be an important target for novel anti-inflammatory interventional strategies to effectively treat CF lung function decline. This review will consider evidence for the efficacy for anti-inflammatories in the treatment of CF, the potential role of macrophages, and the significance of targeting these pathways at a time when rectifying the basic defect in CF, through use of novel CFTR modulator therapies, is becoming increasingly viable.<br />Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, while evidence is still insufficient. Within the multicentre project "Effects of Low-Level Air Pollution A Study in Europe" (ELAPSE), we examined the associations of long-term exposures to particulate matter with diameter&lt;2.5 µm (PM<br />), nitrogen dioxide (NO<br />), and black carbon (BC) with asthma incidence in adults.<br />We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. [https://www.selleckchem.com/products/xl413-bms-863233.html XL413 cost] The average concentrations of air pollutants in 2010 were modelled by hybrid land use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders.<br />Of 98 326 participants, 1965 developed asthma during a 16.6 years mean follow-up. We observed associations in fully adjusted models with hazard ratios and 95% confidence intervals of 1.22 (1.04-1.43) per 5 μg·m<br />for PM<br />, 1.