Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

Improvements in health status with revefenacin, a once-daily, nebulized, long-acting muscarinic antagonist for chronic obstructive pulmonary disease.

BACKGROUND: Replicate, 12-week, phase 3 trials (0126 and 0127) of once-daily nebulized revefenacin 175 µg vs placebo demonstrated significant bronchodilation and improvements in health status in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). This post hoc analysis evaluated improvement in patient-reported outcomes (PROs), including the St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Clinical COPD Questionnaire (CCQ) in both women and men. METHODS: Participants were pooled from the two 12-week studies (411 [51%] women and 401 [49%] men). Changes in PROs were assessed overall and separately in men and women. RESULTS: Revefenacin improved SGRQ and CAT total scores from baseline in both studies; improvement in CCQ total score reached significance only in 0126. In pooled data, a greater proportion of patients achieved clinically meaningful response in SGRQ score (≥4-unit decrease from baseline) with revefenacin vs placebo (odds ratio, 1.5; 95% confidence interval, 1.1-2.1; P = 0.012). Clinically meaningful responses were also seen in CAT (≥2-unit decrease from baseline) and CCQ (≥0.4-unit decrease from baseline) scores with revefenacin vs placebo. When stratified by sex, improvements from baseline in SGRQ, CAT, and CCQ scores following revefenacin vs placebo reached statistical significance only in women. CONCLUSIONS: Maintenance treatment with revefenacin improved health status in patients with moderate to very severe COPD; however, the effect was more pronounced for women than men. CLINICALTRIALS: GOV: NCT02459080; NCT02512510.

Lung deposition of inhaled once-daily long-acting muscarinic antagonists via standard jet nebulizer or dry powder inhaler, measured using functional respiratory imaging, in patients with chronic obstructive pulmonary disease.

BACKGROUND: Data for bronchodilator deposition via nebulizers and dry powder inhalers (DPIs) in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD) are limited. We used functional respiratory imaging (FRI) to determine deposition patterns for revefenacin solution via a PARI LC® Sprint® nebulizer and tiotropium powder via HandiHaler® DPI. METHODS: Ten patients with COPD, of whom 9 had severe airflow obstruction, were selected from FLUIDDA's database. The study did not enroll patients. Drug deposition in the extrathoracic and intrathoracic regions, including the central and peripheral airways was simulated by FRI. The percentage of delivered dose and central-to-peripheral (C/P) deposition ratio for nebulizer and DPI were evaluated. RESULTS: Mean ±â€„standard deviation (SD) age was 64.7 ±â€„7.1 years, height was 168.8 ±â€„8.5 cm, and percent predicted forced expiratory volume in 1 s was 40.8 ±â€„12.3%; 50% of patients were men. At optimal inhalation flow, intrathoracic and peripheral deposition was three-fold higher for revefenacin via nebulizer than tiotropium via HandiHaler (mean ±â€„SD 34.6 ±â€„8.53% versus 10.9 ±â€„5.67% and 18.2 ±â€„4.30% versus 5.8 ±â€„2.73% of delivered dose, respectively). Similar results were observed for suboptimal flow (mean ±â€„SD percentage of revefenacin versus tiotropium: intrathoracic, 32.1 ±â€„8.3% versus 15.1 ±â€„5.9%; peripheral; 16.6 ±â€„4.1% versus 8.4 ±â€„2.9%). The C/P deposition ratio for nebulizer was similar to DPI (mean ±â€„SD 0.915 ±â€„0.241 versus 0.812 ±â€„0.249 at optimal; 0.947 ±â€„0.253 versus 0.784 ±â€„0.219 at suboptimal flow), even though the mass median aerodynamic diameter of revefenacin was higher than tiotropium. C/P deposition ratio for revefenacin decreased after bronchodilation (0.915 ±â€„0.241 pre-bronchodilation versus 0.799 ±â€„0.192 post-bronchodilation), suggesting progressively better deposition in the peripheral region, assuming bronchodilation occurred during the nebulization process. CONCLUSIONS: These results demonstrate more efficient intrathoracic and peripheral deposition for revefenacin via standard jet nebulizer than tiotropium via HandiHaler, with similar C/P deposition ratio in patients with COPD. Nebulizers are an efficient alternative to DPIs for bronchodilator administration in patients with COPD.