In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer.

Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3, POSTN, PPARD, STAT1, MYC, CD44, and FOSB. The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients (n = 1925) was assessed using a Kaplan-Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone.

Asthma severity as a contributing factor to cancer incidence: A cohort study.

BACKGROUND: A putative link between asthma and asthma severity with the occurrence of cancer has been suggested but has not been fully investigated. The objective of this study is to assess the incidence of all types of cancer in a cohort of asthmatic patients. METHODS AND FINDINGS: A single center cohort retrospective study was conducted to investigate the role of asthma as a potential risk factor for various cancers. Participants were followed for a period of 9 years from 01/01/2010 to 30/12/2018 and cancer incidence and its determinants were collected in asthmatic patients and controls from the same population source but without any respiratory disease. Overall, 2,027 asthma patients and 1,637 controls were followed up for an average of 9 years. The statistical analysis showed that 2% of asthma patients were diagnosed with various cancers, resulting in an incidence rate of cancer of 383.02 per 100,000 persons per year which is significantly higher than the 139.01 per 100,000 persons per year observed in matched controls (p-value < 0.001). The top four cancers reported among asthmatics were breast, colon, lung and prostate cancer. Lung cancer in asthmatics had the longest diagnosis period with a mean of 36.6 years compared to the shortest with prostate cancer with 16.5 years. CONCLUSIONS: This study shows that asthma patients are at increased risk of different types of cancers with asthma severity and goiter as the main factors that may increase the risk of developing cancers among asthmatic patients.

Acute Management and Long-Term Survival Among Subjects With Severe Middle East Respiratory Syndrome Coronavirus Pneumonia and ARDS.

BACKGROUND: Data on the management, clinical course, and outcome of critical patients with Middle East Respiratory Syndrome coronavirus are scarce. We report here our experience and long-term outcome of such patients. METHODS: Subjects intubated for management of ARDS from Middle East Respiratory Syndrome coronavirus pneumonia and ARDS during the April-May 2014 outbreak were included. Their characteristics, ICU course, management, and outcome were evaluated. RESULTS: Fourteen subjects, including 3 health-care workers, met study criteria. Besides 2 health-care workers, all subjects had comorbidities. Predominant symptoms were fever, cough, and dyspnea. The worst median PaO2 /FIO2 ratio of 118 post-intubation was seen on the third day, and median APACHE II score was 27. All subjects received lung-protective ventilation and 1 mg/kg/d methylprednisolone infusion for ARDS. Eleven subjects received ribavirin and peginterferon α-2a. Subjects had a critical ICU course and required neuromuscular blockade (n = 11; 79%), required rescue therapy for respiratory failure (n = 8; 57%), developed shock (n = 10; 71%), and required renal replacement therapy (n = 8; 57%). Declining C-reactive protein levels correlated with clinical improvement despite continued positive real-time polymerase chain reaction results. Nine subjects died in ICU. Five subjects, including 3 health-care workers, were discharged from hospital and were alive after 1 y. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus pneumonia with ARDS has high mortality in subjects with comorbidities. The mainstay of treatment is meticulous ARDS management. Those who survived the acute infection and its complications remained well after 1 y in our study. The role of ribavirin and interferon warrants urgent further evaluation.