Pulmonary expansion manoeuvres compared to usual care on ventilatory mechanics, oxygenation, length of mechanical ventilation and hospital stay, extubation, atelectasis, and mortality of patients in mechanical ventilation: A randomized clinical trial

by Karina da Silva, Cristino Carneiro Oliveira, Leandro Ferracini Cabral, Carla Malaguti, Anderson José

Pulmonary expansion manoeuvres are therapeutic techniques used to prevent and reverse atelectasis; however, no randomized controlled trials have provided evidence supporting the use of this intervention among individuals on mechanical ventilation. Objective: To evaluate the effects of chest compression-decompression and chest block manoeuvres compared to usual care among patients on mechanical ventilation. Methods: The current study was a randomized clinical trial of adult subjects on mechanical ventilation for 12 to 48 hours. The control group received usual care (passive or active mobilization, manoeuvres for airway clearance and tracheal aspiration). The intervention group received usual care plus two lung expansion manoeuvres, i.e., chest decompression and chest block, while remaining on mechanical ventilation. Assessments were performed before and after usual care, immediately after the intervention and 30 minutes after the intervention. The primary outcome was static compliance. The secondary outcomes were the incidence of atelectasis, dynamic compliance, airway resistance, driving pressure, oxygenation, duration of mechanical ventilation, extubation success, length of hospital and ICU stay, and mortality. Results: Fifty-one participants (67±15 years old, 53% men, 26 in the control group and 25 in the intervention group) were evaluated. No differences in static compliance were observed between groups (intervention minus control) before and after expansion manoeuvres [3.64 ml/cmH₂O (95% CI: -0.36–7.65, p = 0.074)]. Peripheral oxygen saturation differed between groups before and after expansion manoeuvres, with more favourable outcome observed in the control group [-1.04% (95% CI: -1.94 –-0.14), p = 0.027]. No differences were found in other outcomes. Conclusion: Chest compression-decompression and chest block manoeuvres did not improve ventilatory mechanics, the incidence of atelectasis, oxygenation, the duration of mechanical ventilation, the length of stay in the ICU and hospital, or mortality in individuals on mechanical ventilation. The findings of this study can be valuable for guiding evidence-based clinical practice and developing a therapeutic approach that provides real benefits for this population.

Prime editing-mediated correction of the <i>CFTR</i> W1282X mutation in iPSCs and derived airway epithelial cells

by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

Perceptions of individuals regarding barriers to participation in a pulmonary rehabilitation program after hospitalization due to COVID-19: A qualitative study

by Rafaella Rabelo Polato, Cristino Carneiro Oliveira, Yuri Augusto de Sousa Miranda, Leandro Ferracini Cabral, Carla Malaguti, Anderson José

Introduction

Several individuals with post-COVID-19 syndrome referred for pulmonary rehabilitation did not participate. This study aimed to explore individuals’ barriers to participating in posthospitalization COVID-19 rehabilitation.

Materials and methods

This was a qualitative, multicenter study performed using semistructured interviews. This study included 20 individuals hospitalized for COVID-19 who refused to participate in a pulmonary rehabilitation program at a university hospital.

Results

Individuals reported difficulties accessing the rehabilitation center, mainly due to distance, transport costs and conditions, and lack of companions. Health problems (e.g., surgeries, pain, and mobility difficulties) and lack of time due to work, commuting, and household work were also reported. Another reported theme was not perceiving the need for rehabilitation due to feeling well. Minor themes included the need for more information about rehabilitation and a lack of interest, motivation, and medical encouragement.

Conclusion

Individuals hospitalized for COVID-19 faced several barriers to participating in a pulmonary rehabilitation program. These barriers included difficulties in accessing the rehabilitation center, health problems, lack of time, and the perception that rehabilitation was unnecessary. There is a need for actions to overcome these barriers to make the program available to a larger number of individuals.