In severe eosinophilic asthma controlled with benralizumab, tapering high-dose ICS reduced dose while maintaining control.

SOURCE CITATION: Jackson DJ, Heaney LG, Humbert M, et al; SHAMAL Investigators. Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study. Lancet. 2024;403:271-281. 38071986.

Designing and validating an experimental protocol to induce airway narrowing in older adults with and without asthma.

BACKGROUND: Persons with asthma may experience excessive airway narrowing due to exercise or exposure to cold air, worsening their daily functionality. Exercise has several benefits for asthma control, but it may induce airway narrowing in some persons with asthma. When combined with cold temperatures, it introduces another layer of challenges. Therefore, managing this interaction is crucial to increase the quality of life in individuals with asthma. The purpose of this study was to develop a reliable experimental protocol to assess the effects of exercise and cold air on airway narrowing in adults with asthma in a controlled and safe environment. METHODS: This study was a randomized cross-over study in adults with and without asthma. Participants underwent a protocol involving a 10-min seated rest, followed by a 10-min cycling on a stationary bike in different temperatures of 0, 10, or 20  ∘ C. The sequence of room temperatures was randomized, and there was a 30-min interval for recovery between each temperature transition. In each temperature, to measure lung function and respiratory symptoms, oscillometry and a questionnaire were used at 0 min (baseline), after 10 min of sitting and before starting biking (pre-exercise), and after 10 min of biking (post-exercise). At each room temperature, the changes in airway mechanics and asthma symptoms among baseline, pre-exercise, and post-exercise were compared with one-way repeated measures ANOVA or Friedman Rank Test. Within each arm, cardiac and thoraco-abdominal motion respiration signals were also measured continuously using electrodes and calibrated respiratory inductance plethysmographs, respectively. RESULTS: A total of 23 persons with asthma (11 females, age: 56.3 ± 10.9 years, BMI: 27.4 ± 5.7 kg/m2) and 6 healthy subjects (3 females, age: 61.8 ± 9.1 years, BMI: 28.5 ± 3.1 kg/m2) were enrolled in the study. Cold temperature of 0 ∘ C induced airway narrowing in those with and without asthma after 10 and 20 min, respectively. Exercise intervention had significant changes in airway narrowing in participants with asthma in the range of 10-20 ∘ C. Our results showed that in asthma, changes in subjective respiratory symptoms were due to both cold temperatures of 0 and 10 ∘ C and exercise in the 0-20 ∘ C range. Respiratory symptoms were not noticed among the healthy participants. CONCLUSION: In conclusion, our findings suggest that exposure to cold temperatures of 0 ∘ C could serve as a reliable method in the experimental protocol for inducing airway narrowing in asthma. The impact of exercise on airway narrowing was more variable among participants. Understanding these triggers in the experimental protocol is essential for the successful management of asthma in future studies.

A pilot study to assess the effects of preventing fluid retention in the legs by wearing compression stockings on overnight airway narrowing in mild asthma.

PURPOSE: Nocturnal asthma is a sign of asthma worsening and could be partially due to more fluid drawn into the thorax during sleep by gravitational force and/or pharyngeal collapse in those with obstructive sleep apnea. Wearing compression stockings during the day reduces fluid shift from the legs to the neck overnight. However, the potential effect of wearing compression stockings to reduce fluid accumulation in the leg and to improve nocturnal small airway narrowing in patients with asthma has not been investigated. This study investigates whether reducing leg fluid volume by wearing compression stockings during the day would attenuate small airway narrowing in patients with asthma before and after sleep. METHODS: We enrolled 11 participants with asthma. All participants underwent overnight polysomnography with or without wearing compression stockings for 2 weeks. Before and after sleep, leg fluid volume (LFV) was measured by bioelectrical impedance, and airway narrowing was primarily assessed by respiratory system resistance and reactance at 5 Hz (R5 and X5 respectively) using oscillometry. RESULTS: After 2 weeks of wearing compression stockings, the LFV measured in the evening was reduced (∆ = - 192.6 ± 248.3 ml, p = 0.02), and R5 and X5 improved (∆ = - 0.7 ± 0.9 cmH2O/L/s, p = 0.03 and 0.2 ± 1.4 cmH2O/L/s, p = 0.05 respectively). No changes were observed in the morning. CONCLUSIONS: Preventing fluid retention in the legs by wearing compression stockings for 2 weeks during the day, reduced LFV and airway narrowing in the evening in all participants with asthma, but not in the morning after sleep.

In Black and Latinx patients, as-needed inhaled glucocorticoids reduced asthma exacerbations at 15 mo.

SOURCE CITATION: Israel E, Cardet JC, Carroll JK, et al. Reliever-triggered inhaled glucocorticoid in Black and Latinx adults with asthma. N Engl J Med. 2022;386:1505-18. 35213105.

Prescription Pathways from Initial Medication Use to Triple Therapy in Older COPD Patients: A Real-World Population Study.

BACKGROUND AND OBJECTIVE: Triple therapy with an inhaled corticosteroid (ICS), a long-acting ß2-agonist bronchodilator (LABA) and a long-acting muscarinic antagonist (LAMA) is recommended as step-up therapy for chronic obstructive pulmonary disease (COPD) patients who continue to have persistent symptoms and increased risk of exacerbation despite treatment with dual therapy. We sought to evaluate different treatment pathways through which COPD patients were escalated to triple therapy. METHODS: We used population health databases from Ontario, Canada to identify individuals aged 66 or older with COPD who started triple therapy between 2014 and 2017. Median time from diagnosis to triple therapy was estimated using the Kaplan-Meier method. We classified treatment pathways based on treatments received prior to triple therapy and evaluated whether pathways differed by exacerbation history, blood eosinophil counts or time period. RESULTS: Among 4108 COPD patients initiating triple therapy, only 41.2% had a COPD exacerbation in the year prior. The three most common pathways were triple therapy as initial treatment (32.5%), LAMA to triple therapy (29.8%), and ICS + LABA to triple therapy (15.4%). Median time from diagnosis to triple therapy was 362 days (95% confidence interval:331-393 days) overall, but 14 days (95% CI 12-17 days) in the triple therapy as initial treatment pathway. This pathway was least likely to contain patients with frequent or severe exacerbations (22.0% vs. 31.5%, p < 0.001) or with blood eosinophil counts ≥300 cells/µL (18.9% vs. 22.0%, p < 0.001). CONCLUSION: Real-world prescription of triple therapy often does not follow COPD guidelines in terms of disease severity and prior treatments attempted.

Home noninvasive positive-pressure ventilation reduces mortality and intubations in COPD with hypercapnia.

SOURCE CITATION: Wilson ME, Dobler CC, Morrow AS, et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2020;323:455-65. 32016309.

Changes in Oxyhemoglobin Concentration in the Prefrontal Cortex during Cognitive-Motor Dual Tasks in People with Chronic Obstructive Pulmonary Disease.

Cognitive and motor impairment are well documented in chronic obstructive pulmonary disease (COPD) patients, but their relationship has not been studied. This study evaluated and compared cognitive and motor performance during dual tasks and related dorsolateral prefrontal cortex (PFC) changes in oxygenated hemoglobin (ΔO2Hb), a proxy measure of neural activity, in patients with COPD and age-matched healthy individuals. Participants performed three single tasks: (1) backwards spelling cognitive task; (2) 30 m preferred paced walk; (3) 30 m fast walk, and two dual tasks: (4) preferred paced walk + backwards spelling; (5) fast paced walk + backwards spelling. The ΔO2Hb from left and right dorsolateral PFC were measured using functional near-infrared spectroscopy. Gait velocity was measured using a Zeno walkway. Compared to healthy adults (n = 20), patients with COPD (n = 15) had higher ΔO2Hb during single preferred (-0.344 ± 0.185 vs. 0.325 ± 0.208 µM; p = 0.011) and fast paced walk (-0.249 ± 0.120 vs. 0.486 ± 0.182 µM; p = 0.001) in right PFC. Among healthy adults, ΔO2Hb were higher bilaterally during preferred paced walking dual versus single task (right: 0.096 ± 0.159 vs. -0.344 ± 0.185 µM, p = 0.013; left: 0.114 ± 0.150 vs. -0.257 ± 0.175 µM, p = 0.049) and in right PFC during fast walking dual versus single task (0.102 ± 0.228 vs. -0.249 ± 0.120, p = 0.021). Patients with COPD did not increase O2Hb during dual versus single tasks. Patients with COPD exhibited slower velocity than older adults during all walking tasks. The lack of further increase in O2Hb from single to dual tasks in patients with COPD, may indicate reduced cognitive-motor capacity and contribute to poorer motor performance limiting safe ambulation. Dual tasking rehabilitation may improve neural efficiency to offset these risks.

Epidemiology and health outcomes of sarcoidosis in a universal healthcare population: a cohort study.

Sarcoidosis-related mortality appears to be rising in North America, with increasing rates in females and the elderly. We aimed to estimate trends in sarcoidosis incidence, prevalence and mortality in Ontario, Canada.We performed a cohort study using health administrative data from Ontario between 1996 and 2015. International Classification of Diseases and Ontario Health Insurance Plan codes were used for case detection. Three disease definitions were created: 1) sarcoidosis, two or more physician claims within 2 years; 2) chronic sarcoidosis, five or more physician claims within 3 years; and 3) sarcoidosis with histology, two or more physician claims with a tissue biopsy performed between claims.Overall, 18 550, 9199 and 3819 individuals with sarcoidosis, chronic sarcoidosis and sarcoidosis with histology, respectively, were identified. The prevalence of sarcoidosis was 143 per 100 000 in 2015, increasing by 116% (p<0.0001) from 1996. The increase in age-adjusted prevalence was higher in males than females (136% versus 99%; p<0.0001). The incidence of sarcoidosis declined from 7.9 to 6.8 per 100 000 between 1996 and 2014 (15% decrease; p=0.0009). A 30.3% decrease in incidence was seen among females (p<0.0001) compared with a 5.5% increase in males (p=0.47). Age- and sex-adjusted mortality rates of patients with sarcoidosis rose from 1.15% to 1.47% between 1996 and 2015 (28% increase; p=0.02), with the overall trend being nonsignificant (p=0.39). Mortality rates in patients with chronic sarcoidosis increased significantly over the study period (p=0.0008).The prevalence of sarcoidosis is rising in Ontario, with an apparent shifting trend in disease burden from females to males. Mortality is increasing in patients with chronic sarcoidosis.

End-of-Life Strategies among Patients with Advanced Chronic Obstructive Pulmonary Disease.

RATIONALE: The burden of advanced chronic obstructive pulmonary disease (COPD) is high globally; however, little is known about how often end-of-life strategies are used by this population. OBJECTIVES: To describe trends in the use of end-of-life care strategies by people with advanced COPD in Ontario, Canada. METHODS: A population-based repeated cross-sectional study examining end-of-life care strategies in individuals with advanced COPD was conducted. Annual proportions of individuals who received formal palliative care, long-term oxygen therapy, or opioids from 2004 to 2014 were determined. Results were age and sex standardized and stratified by age, sex, socioeconomic status, urban/rural residence, and immigrant status. Measurement/Main Results: There were 151,912 persons with advanced COPD in Ontario between 2004 and 2014. Use of formal palliative care services increased 1% per year from 5.3% in 2004 to 14.3% in 2014 (P value for trend < 0.001), whereas use of long-term oxygen therapy increased 1.1% per year from 26.4% in 2004 to 35.3% in 2013 (P value for trend < 0.001). The use of opioids was relatively stable (40.0% in 2004 and 41.8% in 2014; P value for trend = 0.08). Younger individuals were less likely to use formal palliative care services and long-term oxygen therapy. Males were less likely than females to receive long-term oxygen therapy and opioids. CONCLUSIONS: The proportion of people with advanced COPD using end-of-life strategies, although increasing, remains low. Efforts should focus on increasing access to such strategies and educating patients and providers of their benefits.

Real-world health care utilization and effectiveness of omalizumab for the treatment of severe asthma.

BACKGROUND: Omalizumab is indicated for the treatment of moderate to severe asthma. There is limited observational evidence on the costs and effectiveness of omalizumab. OBJECTIVE: To examine the costs and effectiveness of omalizumab for treatment of severe asthma relative to nonusers. METHODS: We conducted a within-person repeated-measures matched cohort study in Ontario, Canada from April 1, 2012 to March 31, 2014. Continuous users of omalizumab were matched with up to 4 nonusers according to age, sex, recent specialist visits, oral corticosteroid use, asthma severity, and Charlson comorbidity score. The primary outcome was direct health care costs. Secondary outcomes were asthma-related hospitalizations or emergency department visits and oral corticosteroid use. The association between omalizumab use and each outcome was assessed using mixed-effects models adjusting for confounders. RESULTS: Ninety-five omalizumab users and 352 nonusers were matched. Among users, there was a significant increase in health care costs of $1,796 per person owing to the cost of the medication at treatment initiation (P < .0001). Costs did not change significantly among nonusers ($85 increase in average monthly costs per person; P = .59). We found no significant changes in the rates of asthma-related hospitalizations or emergency department visits among omalizumab users (P = .44) or nonusers (P = .99) between pre- and postintervention periods. CONCLUSION: The use of omalizumab was associated with increased costs but no evidence of lower rates of clinically important outcomes. These results suggest omalizumab had limited effectiveness in our study population. Future studies should further explore subsets of patients most likely to benefit from omalizumab therapy.

Outcomes of patients with chronic obstructive pulmonary disease diagnosed with or without pulmonary function testing.

BACKGROUND: A small number of people with chronic obstructive pulmonary disease (COPD) receive pulmonary function testing around the time of diagnosis. Because omitting testing increases misdiagnosis, we sought to determine whether health outcomes differed between patients whose COPD was diagnosed with or without pulmonary function testing. METHODS: We conducted a longitudinal population study of patients with physician-diagnosed COPD from 2005 to 2012 using health administrative data from Ontario, Canada. We assessed whether having pulmonary function testing around the time of diagnosis was associated with the composite outcome of admission to hospital for COPD or all-cause death, using adjusted survival analysis. RESULTS: Chronic obstructive pulmonary disease was diagnosed in 68 898 patients during the study period; 41.2% of patients received peridiagnostic pulmonary function testing. In adjusted analysis, patients who underwent testing were less likely to die or be admitted to hospital for COPD (adjusted hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.89-0.94) and were more likely to be prescribed an inhaled long-acting bronchodilator than patients who did not undergo testing. Subgroup analysis suggested that the association of testing and outcomes was confined to patients with COPD diagnosed in the ambulatory care setting (adjusted HR 0.80, 95% CI 0.76-0.84). INTERPRETATION: Confirmation of a COPD diagnosis using pulmonary function testing is associated with a decreased risk of death and admission to hospital for COPD. In ambulatory patients, this effect may be from increased use of appropriate COPD medications. The findings of this study validate current guideline recommendations that encourage pulmonary function testing for diagnosis in all patients with suspected COPD.