Background: Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD. Methods: Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry. Measurements and main results: Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R2 achieved was 0.7 with mean square error of 0.13. Conclusion: In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy. Trial registration: clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114
Introduction: Recombinant human deoxyribonuclease I (rhDNase) cleaves DNA in mucus, facilitating increased mucociliary clearance of purulent sputum. In cystic fibrosis (CF), rhDNase improves pulmonary function and decreases exacerbations. Conversely, rhDNase use in non-CF bronchiectasis (NCFB) patients has not yielded similarly effective results. We explored the safety and feasibility of rhDNase in patients with bronchiectasis due to primary ciliary dyskinesia (PCD). Methods: In this real-life pilot study, patients with PCD received rhDNase to treat viscous mucus. We compared pulmonary function tests and pulmonary exacerbations for these patients over six months of use of rhDNase. Results: Eight PCD patients with symptomatic bronchiectasis commenced use of rhDNase at variable dosing (ranging from at least twice weekly to a full 2.5 mg dose daily). Over a six-month period, pulmonary function tests, as measured by mean FVC and FEV1, remained relatively stable compared to prior to commencing rhDNase. Mean pulmonary exacerbations decreased from 3.1 to 2.3 in the six-month period after commencing rhDNase, as compared to the six-month period prior to rhDNase. Conclusions: Use of rhDNase in PCD patients was safe and did not adversely impact lung function or increase pulmonary exacerbations, in contrast to earlier trial results in NCFB patients with heterogeneous etiologies. Further clinical data is required to identify the population of PCD patients who can benefit from rhDNase, as well as the appropriate dosing and timing.
Two doses of mRNA SARS-CoV-2 vaccines elicit an attenuated humoral immune response among immunocompromised patients. Our study aimed to assess the immunogenicity of a third dose of the BNT162b2 vaccine among lung transplant recipients (LTRs). We prospectively evaluated the humoral response by measuring anti-spike SARS-CoV-2 and neutralizing antibodies in 139 vaccinated LTRs ~4–6 weeks following the third vaccine dose. The t-cell response was evaluated by IFNγ assay. The primary outcome was the seropositivity rate following the third vaccine dose. Secondary outcomes included: positive neutralizing antibody and cellular immune response rate, adverse events, and COVID-19 infections. Results were compared to a control group of 41 healthcare workers. Among LTRs, 42.4% had a seropositive antibody titer, and 17.2% had a positive t-cell response. Seropositivity was associated with younger age (t = 3.736, p < 0.001), higher GFR (t = 2.355, p = 0.011), and longer duration from transplantation (t = −1.992, p = 0.024). Antibody titer positively correlated with neutralizing antibodies (r = 0.955, p < 0.001). The current study may suggest the enhancement of immunogenicity by using booster doses. Since monoclonal antibodies have limited effectiveness against prevalent sub-variants and LTRs are prone to severe COVID-19 morbidity, vaccination remains crucial for this vulnerable population.
PwCF carrying the Q359K/T360K variant may have significant clinical benefit from treatment with ETI that may exceed improvements observed with TI treatment. These data support routine clinical use of ETI in this rare patient group. https://bit.ly/45DjFw9.