Maselli, Diego J

Abstract Introduction Persistent dyspnea increases the risk of disability and impairs quality of life in older patients with bronchiectasis. The impact of dyspnea and fatigue on patients with bronchiectasis in long term follow-up has not been adequately established. We sought to determine if fatigue and higher-grade dyspnea are associated with worse clinical outcomes in 5-years of longitudinal follow-up. Methods We analyzed data collected from a prospective cohort of adult patients with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry. Patients with a modified Medical Research Council (mMRC) dyspnea score collected at baseline and during 3-5 years of follow-up were included and stratified as mMRC<2 versus mMRC ≥2. Kruskal-Wallis, independent sample t-tests and chi-square tests were used to test the differences in medians and means for continuous variables and associations between categorical variables, respectively, between the baseline mMRC groups and bronchiectasis severity index (BSI) components at follow-up. A multivariable logistic regression analysis was performed to determine the association between dyspnea and clinical outcomes (exacerbations and hospitalizations) at follow-up. Results 1185 adult patients with bronchiectasis met the inclusion criteria. The median age (interquartile range) was 76 (68 to 83) years. At baseline, patients with mMRC ≥2 had a higher proportion of co-existing diagnoses such as asthma, chronic obstructive pulmonary disease (COPD), otitis/rhinosinusitis, rheumatologic disease, and pneumonia compared to patients with mMRC <2 (all p<0.05, data not shown). Furthermore, patients with mMRC > 2 compared to patients with mMRC <2 had higher prevalence of fatigue, acute exacerbations and pulmonary related hospitalizations, and lower mean percentage predicted forced expiratory volume in one second (FEV1) at follow-up (all p< 0.05) (Table 1). Interestingly, body mass index was slightly higher among those with baseline mMRC ≥2 compared to mMRC <2 (p=0.02). Among those with mMRC ≥2 at both baseline and follow-up (n=67, 42%), the odds of having ≥1 exacerbation was 2.4 times higher (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.45-4.1) and 2.8 times higher for ≥1 hospitalization (OR 2.8, 95% CI 1.45-5.2) during follow-up after adjusting for fatigue. Conclusion Elevated dyspnea was associated with a greater proportion of patients with bronchiectasis exhibiting acute exacerbations and pulmonary related hospitalizations and lower lung function during follow-up. Research is still needed to understand the causes (drivers) of dyspnea to implement better treatment strategies and reduce adverse outcomes in bronchiectasis patients.

Abstract Rationale Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

Abstract Background Optimization of mechanical ventilation (MV) in patients with cardiac arrest (CA) may help improve outcomes in these patients. We sought to investigate the association between hyperoxia, PCO2, and positive end-expiratory pressure (PEEP) with mortality in patients with CA. Methods Patients admitted to our medical center CICU from 2001 through 2012 (MIMIC-III database) who received MV with available information on MV parameters and had arterial blood gases sampling were included. Hyperoxia was defined as time-weighted mean of PaO2 >120 mmHg and non-hyperoxia as PaO2 ≤120 mmHg, while Hypercarbia was defined as PCO2 >35 mmHg during CICU admission. The primary outcome was in-hospital mortality. Multivariable logistic regression was used to assess the association between hyperoxia and in-hospital mortality adjusted for age, female sex, Oxford Acute Severity of Illness Score, creatinine, lactate, pH, PaO2/FiO2 ratio, PCO2, PEEP, and time spent on PEEP. Results Among 136 patients, PaO2 = 139±55 mmHg, PCO2 = 39±10 mmHg, and PEEP = 6.4±2.2cmH2O. Unadjusted mortality was higher in the hyperoxic group (51.4%) compared to the non-hyperoxic group (29.0%) (long rank test p=0.0034, figure). In multivariable analysis, hyperoxia was independently associated with higher in-hospital mortality (OR 4.046, 95% CI: 1.501–10.907, p=0.0057). Additionally, there was no association between the presence of hypercarbia and in-hospital mortality (OR 0.896, 95% CI: 0.319 to 2.521, p=0.836) nor when PCO2 was analyzed as a continuous variable (OR 1.063 per 1 mmHg increase in CO2, 95% CI: 0.111–10.145, p=0.957). Similarly, there was no assocation between PEEP and in-hospital mortality (OR 1.012 per 1cmH2O increase, 95% CI: 0.807 to 1.270, p=0.917). Post-hoc analysis with PaO2 as a continuous variable was consistent with the primary analysis (OR 1.214 per 10 mmHg increase in PaO2, 95% CI: 1.059–1.391, p=0.005). Conclusions In patients with CA, hyperoxia was associated with increased mortality, while PCO2 and PEEP levels were not. Optimal MV parameters are important in the management of patients with CA. Further research is warranted to confirm this association and explore the mechanisms behind these observations. These studies can help establish the best MV strategies for patients with CA. Funding Acknowledgement Type of funding source: None