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Cystic fibrosis is a genetic pathology characterized by abnormal accumulation of mucus in the respiratory, gastrointestinal, and reproductive tracts, caused by mutations in the CFTR gene. Although the classical presentation of the condition is well known, there is still a need for a better characterization of metabolic alterations related to cystic fibrosis and different genotypic mutations. We employed untargeted, comprehensive lipidomics of blood serum samples to investigate alterations in the lipid metabolism related to the pathology, mutation classes, and lung function decline. Six unique biomarker candidates were able to independently differentiate diseased individuals from healthy controls with excellent performance. Cystic fibrosis patients showed dyslipidemia for most lipid subclasses, with significantly elevated odd-chain and polyunsaturated fatty acyl lipids. Phosphatidic acids and diacylglycerols were particularly affected by different genotypic mutation classes. We selected a biomarker panel composed of four lipids, including two ceramides, one sphingomyelin, and one fatty acid, which correctly classified all validation samples from classes III and IV. A biomarker panel of five oxidized lipids was further selected to differentiate patients with reduced lung function, measured as predicted FEV1%. Our results indicate that cystic fibrosis is deeply related to lipid metabolism and provide new clues for the investigation of the disease mechanisms and therapeutic targets.

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BACKGROUND: Dynamic X-ray (DXR) provides images of multiple phases of breath with less radiation exposure than CT. The exact images at end-inspiratory or end-expiratory phases can be chosen accurately. PURPOSE: To investigate the correlation of the projected lung area (PLA) by dynamic chest X-ray with pulmonary functions. MATERIAL AND METHODS: One hundred sixty-two healthy volunteers who received medical check-ups for health screening were included in this study. All subjects underwent DXR in both posteroanterior (PA) and lateral views and pulmonary function tests on the same day. All the volunteers took several tidal breaths before one forced breath as instructed. The outlines of lungs were contoured manually on the workstation with reference to the motion of diaphragm and the graph of pixel values. The PLAs were calculated automatically, and correlations with pulmonary functions and demographic data were analyzed statistically. RESULTS: The PLAs have correlation with physical characteristics, including height, weight and BMI, and pulmonary functions such as vital capacity (VC) and forced expiratory volume in one second (FEV1). VC and FEV1 revealed moderate correlation with the PLAs of PA view in forced inspiratory phase (VC: right, r = 0.65; left, r = 0.69. FEV1: right, r = 0.54; left, r = 0.59). Multivariate analysis showed that body mass index (BMI), sex and VC were considered independent correlation factors, respectively. CONCLUSION: PLA showed statistically significant correlation with pulmonary functions. Our results indicate DXR has a possibility to serve as an alternate method for pulmonary function tests in subjects requiring contact inhibition including patients with suspected or confirmed covid-19.

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BACKGROUND: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies. OBJECTIVE: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort. METHODS: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline. RESULTS: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.

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Cystic fibrosis (CF) causes airways obstruction and a decline in percent predicted forced expiratory volume in 1 s (FEV1%). FEV1% is an objective measure of a pulmonary exacerbation of CF; improvement in FEV1% is the endpoint used often to determine success of treatment of these acute declines in pulmonary health. Lung Clearance Index (LCI), derived from multiple breath inert gas washout (MBW) test, measures ventilation inhomogeneity and small airways dysfunction. In the United States in 2014-2015, enterovirus D68 (EV-D68), a novel virus, led to hospitalizations in children because of respiratory distress. This report describes 2 patients with CF admitted for pulmonary exacerbations who were enrolled in an inpatient study to assess patient satisfaction and utility of MBW to measure LCI. Diagnostic testing indicated that these patients were infected with EV-D68. Although their FEV1% improved to their previous baseline following treatment for pulmonary exacerbation, it was discordant with LCI. We discuss LCI as a novel measure of pulmonary function and hypothesize that, based on these cases, it may be a more sensitive indicator of ongoing post-viral airways dysfunction as compared to FEV1%.