This large series of patients who received intrapleural tPA/DNase therapy provides important evidence that the treatment is effective and safe, especially as a "rescue therapy" in patients who do not initially respond to antibiotics and thoracostomy drainage.

Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

The lungs of individuals with cystic fibrosis (CF) become chronically infected with that is difficult to eradicate by antibiotic treatment. Two key antibiotic resistance mechanisms are the AmpC β-lactamase that degrades β-lactam antibiotics and MexXYOprM, a three-protein efflux pump that expels aminoglycoside antibiotics from the bacterial cells. Levels of antibiotic resistance gene expression are likely to be a key factor in antibiotic resistance but have not been determined during infection. The aims of this research were to investigate the expression of the and genes during infection in patients with CF and in bacteria isolated from the same patients and grown under laboratory conditions. isolates from 36 CF patients were grown in laboratory culture and gene expression measured by reverse transcription-quantitative PCR (RT-qPCR). The expression of varied over 20,000-fold and that of over 2,000-fold between isolates. The median expression levels of both genes were increased by the presence of subinhibitory concentrations of antibiotics. To measure gene expression during infection, we carried out RT-qPCR using RNA extracted from fresh sputum samples obtained from 31 patients. The expression of varied over 4,000-fold, while expression varied over 100-fold, between patients. Despite these wide variations, median levels of expression of in bacteria in sputum were similar to those in laboratory-grown bacteria. The expression of was higher in sputum than in laboratory-grown bacteria. Overall, our data demonstrate that genes that contribute to antibiotic resistance can be highly expressed in patients, but there is extensive isolate-to-isolate and patient-to-patient variation.

Conflict of interest: Lung Therapeutics Inc. (LTI) sponsored the trial. SI serves as a Founder and Chief Scientific Officer of LTI and a member of the Board of Directors of LTI, which provided funding for preparation of the drug product and for the trial. He has an equity position (first-tier conflict of interest) in the company, as does the University of Texas Horizon Fund and the UTHSCT. He has a conflict-of-interest plan acknowledging and managing these declared conflicts of interest through the UTHSCT and the UT System. He is an inventor on a patent (USPTO 7332469) held by the UT Board of Regents and licensed to LTI. AAK and GF have received funding from LTI for this study, and they and KS likewise have conflict-of-interest management plans at the UTHSCT. KPS has an equity position in LTI. AAK, GF, and SI are inventors on patent USPTO 10,175,255 B2. NR and YCGL serve as key opinion leaders for LTI, and NR is paid for input to the company. SS is a paid consultant for LTI, and JG received payment as medical monitor for the study from LTI. LB has a potential conflict of interest, having more than $50,000 funding support for personnel and laboratory work for this study from LTI. AMS received funding in the fiscal year prior to submission greater than $50,000 from GSK for 2 funded COPD trials. YCGL has led clinical trials for which Rocket Ltd. provided pleural drainage kits for patients without charge. YCGL has served as advisor to LTI and CareFusion/BD.