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1.
Chest ; 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32603714

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal mortality. Overnight deterioration of inspiratory capacity (IC) and forced expiratory volume in 1 second (FEV1) have previously been documented. However, the precise nature of this deterioration and mechanisms by which evening bronchodilators may mitigate this have not been studied. RESEARCH QUESTION: To determine the effect of evening dosing of dual, long-acting bronchodilators on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND). STUDY DESIGN: A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilators (BD; aclidinium bromide/formoterol fumarate dihydrate, 400/12 mcg) or placebo (PL) on morning trough IC (12 hours post-dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics and IND (secondary outcomes). METHODS: 20 participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures and diaphragm electromyography (EMGdi%max; IND) at 6 time points from 20h00-08h00 (i.e. 0-12 hours post-dose) and compared with sleeping IND. RESULTS: Compared with PL, evening BD was not associated with increased morning trough IC 12 hours post-dose (p=0.48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 hours post-dose (AUC 0-12), and IC for 10 hours post-dose were improved (p<0.05). During PL, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with BD treatment (p<0.05) with no change in ventilation or breathing pattern. INTERPRETATION: Respiratory mechanics significantly deteriorated at night during PL. While morning trough IC was unchanged, evening bronchodilator treatment was consistently associated with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo.

2.
J Bras Pneumol ; 46(3): e20200116, 2020 Jun 15.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32556024
3.
Ther Adv Respir Dis ; 14: 1753466620926858, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32482147

RESUMO

BACKGROUND: Exercise tolerance is an important endpoint in chronic obstructive pulmonary disease (COPD) clinical trials. Little is known about the comparative measurement properties of constant work rate cycle ergometry (CWRCE) and the endurance shuttle walking test (ESWT). The objective of this sub-analysis of the TORRACTO® study was to directly compare the endurance measurement properties of CWRCE and ESWT in patients with COPD in a multicentre, multinational setting. We predicted that both tests would be similarly reliable, but that the ESWT would be more responsive to bronchodilation than CWRCE. METHODS: This analysis included 151 patients who performed CWRCE and ESWT at baseline and week 6 after receiving once-daily placebo, tiotropium/olodaterol (T/O) 2.5/5 µg or T/O 5/5 µg. Reproducibility was assessed by comparing their respective performance at baseline and week 6 in the placebo group. Responsiveness to bronchodilation was assessed by comparing endurance time at week 6 with T/O with baseline values and placebo. The locus of symptom limitation and end-exercise Borg scales for breathing and leg discomfort for both tests were also analysed. RESULTS: The intraclass correlation coefficients for CWRCE and ESWT were 0.56 [95% confidence interval (CI) 0.37-0.71] and 0.75 (95% CI 0.63-0.84). More patients were limited by breathing discomfort during the ESWT than during CWRCE, whereas more patients were limited by leg discomfort or breathing/leg discomfort during CWRCE than the ESWT (p <0.0001). Both tests were responsive to bronchodilator treatment: there was a 19% increase in endurance time from baseline at week 6 (p = 0.0006) assessed with CWRCE, and a 20% increase in endurance time assessed with ESWT (p = 0.0013). CONCLUSIONS: Both exercise tests performed well in a multicentre clinical trial. Although the locus of symptom limitation differed between the two tests, both were reliable and responsive to bronchodilation. For future clinical trials, the choice of test should depend on the study requirements. CLINICALTRIALS.GOV IDENTIFIER: NCT01525615. The reviews of this paper are available via the supplemental material section.

4.
Ann Am Thorac Soc ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396385

RESUMO

RATIONALE: Although opioids are frequently prescribed in chronic obstructive pulmonary disease (COPD), there is poor understanding regarding which individuals will experience pulmonary harm upon exposure. OBJECTIVES: We sought to identify patient characteristics and opioid drug properties predictive of opioid-related adverse pulmonary events among older adults with chronic COPD. METHODS: A retrospective, population-based, cohort study design was used, analyzing Ontario heath administrative data. Individuals aged 66 years and older, with validated, physician-diagnosed COPD receiving a new opioid drug were included. Adverse pulmonary events (defined as an emergency room visit, hospitalization or death related to either COPD or pneumonia) occurring within 30 days following new opioid receipt were considered. Multivariable-adjusted, cause-specific hazard modelling was used to identify predictors of adverse pulmonary events. RESULTS: Out of 169,517 older adults with COPD receiving a new opioid, 4861 (2.9%) experienced an adverse pulmonary event within 30 days. Factors independently predisposing to adverse pulmonary events included: older age (>85 years old: hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.26-1.49); long-term care home residence (HR 1.32; 95% CI 1.21-1.44); severe COPD exacerbation within the preceding year (HR 2.96; 95% CI 2.77-3.17); comorbidities (including non-COPD lung disease [HR 1.16; 95% CI 1.09-1.23], congestive heart failure [HR 1.22; 95% CI 1.14-1.30], sleep disorder [HR 1.22; 95% CI 1.15-1.30] and dementia [HR 1.14; 95% CI 1.05-1.24]); other psychoactive medication receipt, including benzodiazepines (HR 1.27; 95% CI 1.19-1.35) and serotonergic antidepressants (HR 1.10; 95% CI 1.03-1.19); and, receipt of an opioid-only agent (HR 1.35; 95% CI 1.26-1.46). Factors that independently protected from adverse pulmonary events included: female sex (HR 0.78; 95% CI 0.73-0.82); surgery within the preceding year (HR 0.70; 95% CI 0.64-0.77); and, musculoskeletal disease (HR 0.75; 95% CI 0.70-0.80). No significant associations were observed between adverse pulmonary events and opioid half-life duration or opioid daily dosage. CONCLUSIONS: Patient and opioid drug factors predictive of opioid-related adverse pulmonary events among older adults with COPD were identified, which may assist with safer opioid prescribing.

5.
Chest ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428514

RESUMO

The lung function laboratory frequently provides relevant information to the practice of Pulmonology. Clinical interpretation of pulmonary function and exercise tests, however, has more recently been complicated by temporal changes in demographics (higher life expectancy) and anthropometric attributes (increased obesity prevalence) and the surge of polypharmacy in a sedentary population suffering from multiple chronic-degenerative diseases. In this narrative review, we concisely discuss some key challenges to testing interpretation which have been impacted from these epidemiological shifts: a) the confounding effects of advanced age and severe obesity, b) the contemporary controversies in the diagnosis of obstruction (including asthma and/or chronic obstructive pulmonary disease), c) the importance of considering the lung diffusing capacity for carbon monoxide (DLCO)/"accessible" alveolar volume (diffusing coefficient, KCO) in association with DLCO to uncover the cause(s) of impaired gas exchange, and d) the modern role of the pulmonary function laboratory (including cardiopulmonary exercise testing) in the investigation of undetermined dyspnea. Following a Bayesian perspective, we suggest interpretative algorithms which consider the pre-test probability of abnormalities as indicated by additional clinical information. We, therefore, adopt a pragmatic approach to help the practicing pulmonologist to apply the information provided by the lung function laboratory to the management of individual patients.

6.
Eur Respir J ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471934

RESUMO

Assessment of dyspnoea severity during incremental cardiopulmonary exercise testing (CPET) has long been hampered by the lack of reference ranges as a function of work rate (WR) and ventilation (V̇E). This is particularly relevant to cycling, a testing modality which overtaxes the leg muscles leading to a heightened sensation of leg discomfort.Reference ranges based on dyspnoea percentiles (0-10 Borg scale) at standardised WRs and V̇E were established in 275 apparently healthy subjects aged 20-85 (131 men). They were compared with values recorded in a randomly selected "validation" sample (N=451, 224 men). Their usefulness in properly uncovering the severity of exertional dyspnoea were tested in 167 subjects under investigation for chronic dyspnoea ("testing sample") who terminated CPET due to leg discomfort (86 men).Iso-WR and, to a lesser extent, iso-V̇E reference ranges (5th-25th, 25th-50th, 50-75th and 75th-95th percentiles) increased as a function of age, being systematically higher in women (p<0.01). There was no significant differences in percentiles distribution between "reference" and "validation" samples (p>0.05). Submaximal dyspnoea-WR scores lied within the 75th-95th or >95th percentiles in 108/118 (91.5%) subjects of the "testing" sample who showed physiological abnormalities known to elicit exertional dyspnoea i.e., ventilatory inefficiency and/or critical inspiratory constraints. In contrast, dyspnoea scores typically lied in the 5th-50th range in subjects without those abnormalities (p<0.001).This frame of reference might prove useful to uncover the severity of exertional dyspnoea in subjects who otherwise would be labeled as "non-dyspneic" while providing mechanistic insights into the genesis of this distressing symptom.

7.
Chest ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304775

RESUMO

BACKGROUND: Massively obese subjects frequently undergo pulmonary function tests nowadays. Obesity-associated decreases in key operating lung volumes (reduced inspiratory capacity and reduced vital capacity) are particularly concerning because they may shorten the "room" for tidal volume expansion with negative physiologic and sensory consequences. RESEARCH QUESTION: Is massive obesity associated with reduced operating lung volumes? If so, is this effect more pronounced in men than women? STUDY DESIGN AND METHODS: We performed an observational, retrospective study in a tertiary, hospital-based laboratory. Pulmonary function test results from 248 super-obese (SO; BMI, 50 to 59.9 kg/m2) and 83 super-super obese (SSO; BMI, ≥60 kg/m2) men and women were analyzed. Electronic medical records were screened to ensure that subjects were free of any disease that potentially could interfere with lung volumes. RESULTS: The prevalence of a low total lung capacity (restriction) was 26.9%, which increased to 38.6% in SSO. Despite the absence of between-sex differences in BMI and spirometric variables derived from the forced maneuver in both SO and SSO, men presented with higher prevalence of restriction (46.7%) than women (19.4%) (P < .05). Between-sex differences in residual volume differed according to the BMI group; SO men presented with higher values than SO women; the opposite was found in the SSO group. The prevalence of restriction with low operating lung volumes was approximately twice (SSO) and approximately thrice (SSO) as high in men compared with women (P < .01). Linear prediction equations as a function of sex, demographic, and anthropometric attributes markedly reduced the prevalence of these abnormalities across the population. INTERPRETATION: Obesity-related restriction leading to low operating lung volumes is highly prevalent in the massively obese subject, particularly in men. These alterations that are associated with massive obesity should be taken into consideration for an accurate interpretation of pulmonary function tests in this growing population.

11.
Respirology ; 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064708

RESUMO

BACKGROUND AND OBJECTIVE: Lack of consensus on diagnosis of ACO limits our understanding of the impact, management and outcomes of ACO. The present observational study aims to describe the prevalence, clinical characteristics and course of individuals with ACO based on various definitions used in clinical practice. METHODS: We included individuals with COPD from the prospective, multisite CanCOLD study and defined subjects with ACO using seven definitions commonly used in the literature. RESULTS: Data including questionnaires, lung function and CT scans were analysed from 522 individuals with COPD who were randomly recruited from the population. Among them, 264 fulfilled at least one of the seven definitions of ACO. Prevalence of ACO varied from 3.8% to 31%. Regardless of the definition, individuals with ACO had worse outcomes (lung function and higher percentage of fast decliners, symptoms and exacerbations, health-related quality of life and comorbidities) than the remaining patients with COPD. Conversely, patients with non-ACO had higher emphysema and bronchiolitis scores. The three definitions that included atopy and/or physician diagnosis of asthma identified subjects who differed significantly from patients with COPD. The two ACO definitions with post-bronchodilator reversibility were concordant with COPD and were the least stable, with less than 50% of the patients from each group maintaining reversibility over visits. CONCLUSION: Atopy and physician-diagnosed asthma are more distinguishing characteristics to identify ACO. This finding needs to be validated using measures of airway inflammation and other specific biomarkers.

12.
Respirology ; 25(2): 134-136, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31769135
13.
Eur Respir J ; 55(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31649067

RESUMO

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V'E)/carbon dioxide output (V'CO2 ) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V'E/V'CO2 ratio in the more dyspnoeic group. V'E/V'CO2 nadir >50 (OR 9.43, 95% CI 5.28-13.6; p=0.0001) and total emphysema extent >15% (2.25, 1.28-3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFEContrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased "wasted" ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.

14.
Respir Care ; 65(4): 444-454, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31719189

RESUMO

BACKGROUND: Severe exertional dyspnea is a commonly reported symptom in patients with COPD, especially in the advanced stages. Our objective was to assess the preliminary impact of comprehensive, individualized management provided by a specialized tertiary center clinic on exertional dyspnea and patient-centered outcomes in patients with advanced COPD. METHODS: This retrospective analysis included 45 subjects with COPD who were evaluated in a newly established dyspnea clinic over 3 years. Those with severe exertional dyspnea (Medical Research Council dyspnea score of ≥4/5), despite optimal disease-targeted therapy were eligible for referral. We used the revised Edmonton Symptom Assessment System (ESAS-r) to assess symptoms. Responders were defined as those whose change from baseline to 2-months met the minimum clinically important difference of ≤-1 in ESAS-r score for shortness of breath. RESULTS: Subjects (mean ± SD age 70 ± 7 years) had an average FEV1 of 36 ± 18% predicted and a Medical Research Council dyspnea score of 4.7 ± 0.4. Responses to the intervention were variable and mean change in the ESAS-r score for shortness of breath in the total group was -0.32 ± 3.39, P = .53. Forty-seven percent of the subjects were identified as responders, and 42, 40, 40, and 33% met the minimum clinically important difference for improvement in ESAS-r scores for tiredness, anxiety, well-being, and depression, respectively. Responders had fewer emergency department annual visits in the 2 years after their first clinic visit compared with nonresponders (mean ± SD, 1.38 ± 1.63 vs 4.45 ± 5.52, P = .034). CONCLUSIONS: Although the impact of our specialized advanced dyspnea clinic was variable, as evaluated by the ESAS-r, it provided measurable additional clinically important benefit to almost half of the subjects with advanced COPD and severe refractory dyspnea.

15.
Adv Ther ; 37(1): 41-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31673990

RESUMO

Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This "dyspnea spiral" is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients' benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand-capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual.

17.
Respir Physiol Neurobiol ; 273: 103322, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31629879

RESUMO

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with pulmonary and extra-pulmonary factors contributing to exercise intolerance. The primary self-reported exercise-limiting symptom may reflect the primary pathophysiological factor contributing to exercise intolerance. We compared physiological and perceptual responses at the symptom-limited peak of incremental cardiopulmonary cycle exercise testing between people with COPD reporting breathlessness (B, n = 34), leg discomfort (LD, n = 16), or a combination of B and LD (BOTH, n = 42) as their main exercise-limiting symptom(s). Despite similarly impaired health status, symptomology and peak exercise capacity, the B group had greater restrictive constraints on tidal volume expansion at end-exercise and was more likely to report unpleasant qualities of exertional breathlessness than LD and BOTH groups. In conclusion, reporting breathlessness as the primary exercise-limiting symptom indicated the presence of distinct lung pathophysiology and symptom perception during exercise in people with COPD.

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