Skeletal muscle dysfunction acquired during critical illness (intensive care unit (ICU)-acquired weakness, ICUAW) plays a pivotal role in clinical outcomes such as liberation from mechanical ventilation, ICU length of stay, hospital length of stay, physical function and mortality.1 2 ICUAW is a common complication of critical illness with a complex aetiology,3 affecting both limb muscles as well as respiratory muscles. The decline in muscle mass is approximately 2%–4% per day in the first week of ICU stay.4 5 Loss of limb muscle mass is more pronounced in patients with multiple organ failure,4 while a rapid decline in diaphragm muscle strength and thickness is associated with sepsis6 and low diaphragm contractile activity.5 Strategies to prevent or treat ICUAW are scarce and mostly focused on the treatment or reduction of risk factors associated with ICUAW...

Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management.Methods

We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+Fe_NO. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer–Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes).

Results

80/611 (13.1%) participants experienced ≥1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and ≥1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer–Lemeshow p value 0.35). Adding spirometry and Fe_NO subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.72 (95% CI 0.70 to 0.73; 71 to 0.74 and 0.71 to 0.73) for the three models, respectively; calibration was best for the spirometry model.

Conclusions

A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of Fe_NO is modest. These models merit an implementation study in clinical practice to assess their utility.

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Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. Blood pressure variability may be a sign of risk of cardiovascular events. The aim of this study was to investigate the hypothesis that severe OSA syndrome is associated with increased blood pressure variability.

Based on respiratory polygraphy, 58 patients were categorized into two groups: severe OSA with apnea/hypopnea index (AHI) greater than 29 episodes per hour (mean 52.2 ± 19.0/h) and mild-to-moderate OSA with AHI between 5 and 30 episodes per hour (mean 20.2 ± 7.8/h). A 24-h noninvasive blood pressure monitoring was performed. The standard deviation of mean blood pressure was used as the indicator of blood pressure variability. In patients with severe, compared with mild-to-moderate OSA, a higher mean nocturnal systolic blood pressure (133.2 ± 17.4 mmHg vs. 117.7 ± 31.2 mmHg, p < 0.05) and diastolic blood pressure (80.9 ± 13.1 mmHg vs. 73.8 ± 9.2, p < 0.01), nocturnal systolic blood pressure variability (12.1 ± 6.0 vs. 7.6 ± 4.3, p < 0.01) and diastolic blood pressure variability (10.5 ± 6.1 vs. 7.3 ± 4.0 p < 0.05), nocturnal mean blood pressure variability (9.1 ± 4.9 mmHg vs. 6.8 ± 3.5 mmHg) were detected.

The findings of the study point to increased nocturnal systolic and diastolic arterial blood pressure and blood pressure variability as risk factors of cardiovascular complications in patients with severe OSA.

Treatment with exogenous alpha-1 antitrypsin (AAT), a potent serine protease inhibitor, was developed originally for chronic obstructive pulmonary disease associated with AAT deficiency; however, other lung conditions involving neutrophilic inflammation and proteolytic tissue injury related to neutrophil elastase and other serine proteases may also be considered for AAT therapy. These conditions include bronchiectasis caused by primary ciliary dyskinesia, cystic fibrosis, and other diseases associated with an increased free elastase activity in the airways.

Inhaled AAT may be a viable option to counteract proteolytic tissue damage. This form of treatment requires efficient drug delivery to the targeted pulmonary compartment. Aerosol technology meeting this requirement is currently available and offers an alternative therapeutic approach to systemic AAT administration. To date, early studies in humans have shown biochemical efficacy and have established the safety of inhaled AAT. However, to bring aerosol AAT therapy to patients, large phase 3 protocols in carefully selected patient populations (i.e., subgroups of patients with AAT deficiency, cystic fibrosis, or other lung diseases with bronchiectasis) will be needed with clinical end points in addition to the measurement of proteolytic activity in the airway.

The outcomes likely will have to include lung function, lung structure assessed by computed tomography imaging, disease exacerbations, health status, and mortality.