Examining the effect of the COVID-19 pandemic on community virus prevalence and healthcare utilisation reveals that peaks in asthma, COPD and respiratory tract infection occur with the re-emergence of rhino/enterovirus.

INTRODUCTION: Airway disease exacerbations are cyclical related to respiratory virus prevalence. The COVID-19 pandemic has been associated with reduced exacerbations possibly related to public health measures and their impact on non-COVID-19 respiratory viruses. We aimed to investigate the prevalence of non-COVID-19 respiratory viruses during the pandemic compared with prior in Ontario, Canada and healthcare utilisation related to asthma, chronic obstructive pulmonary disease (COPD) and respiratory tract infection. METHODS: This is a population-based retrospective analysis of respiratory virus tests, emergency department (ED) visits and hospitalisations between 2015 and 2021 in Ontario. Weekly virus testing data were used to estimate viral prevalence for all non-COVID-19 respiratory viruses. We plotted the %positivity and observed and expected counts of each virus to visualise the impact of the pandemic. We used Poisson and binomial logistic regression models to estimate the change in %positivity, count of positive viral cases and count of healthcare utilisation during the pandemic. RESULTS: The prevalence of all non-COVID-19 respiratory viruses decreased dramatically during the pandemic compared with prior. Comparing periods, the incidence rate ratio (IRR) for positive cases corresponded to a >90% reduction for non-COVID-19 respiratory viruses except adenovirus and rhino/enterovirus. Asthma-related ED visits and hospital admissions fell by 57% (IRR 0.43 (95% CI 0.37 to 0.48)) and 61% (IRR 0.39 (95% CI 0.33 to 0.46)). COPD-related ED visits and admissions fell by 63% (IRR 0.37 (95% CI 0.30 to 0.45)) and 45% (IRR 0.55 (95% CI 0.48 to 0.62)). Respiratory tract infection ED visits and admissions fell by 85% (IRR 0.15 (95% CI 0.10 to 0.22)), and 85% (IRR 0.15 (95% CI 0.09 to 0.24)). Rather than the usual peaks in disease condition, during the pandemic, healthcare utilisation peaked in October when rhino/enterovirus peaked. CONCLUSIONS: The prevalence of nearly all non-COVID-19 respiratory viruses decreased during the pandemic and was associated with marked reductions in ED visits and hospitalisations. The re-emergence of rhino/enterovirus was associated with increased healthcare utilisation.

Functional recovery following hospitalisation of patients diagnosed with COVID-19: a protocol for a longitudinal cohort study.

INTRODUCTION: COVID-19 is an international public health crisis with more than 132 million infections worldwide. Beyond acute infection, emerging data indicate patients diagnosed with COVID-19 may experience persistent sequelae similar to survivors of sepsis or acute respiratory syndromes, including mobility limitations and fatigue. However, there is limited evidence on the trajectory of functional recovery in those hospitalised with COVID-19. The primary aim of the Coronavirus Registry Functional Recovery (COREG-FR) study is to understand the trajectory of functional recovery among individuals hospitalised for COVID-19 over the medium (up to 6 months) and longer term (6-12 months) that will guide clinical care and optimal management of serious COVID-19 illness and recovery. METHODS AND ANALYSIS: COREG-FR is a multicentre longitudinal cohort study. We will enrol a minimum of 211 adults age 18 years and older with COVID-19 from five hospitals. Participants will be followed from admission to hospital as an inpatient, to hospital discharge, and at 3-month, 6-month, 9-month and up to 12-month post-hospital discharge. We will conduct telephone interviews at ward admission and discharge, and telephone interviews plus in-person assessments of physical function and lung function at all remaining follow-ups. Our primary outcome is the Activity Measure for Post-Acute Care mobility scale measured at all time points. We will conduct linear mixed effects regression analyses to explore determinants of functional outcomes after COVID-19 illness. Subgroup analyses based on age (≤65 vs >65 years), frailty status (Clinical Frailty Scale score ≤4 vs >5) and variants of concern will be conducted. ETHICS AND DISSEMINATION: COREG-FR has been approved by Research Ethics Boards at participating sites. We will disseminate this work through peer-reviewed manuscripts, presentations at national and international meetings and through the established COREG website (www.coregontario.ca). COREG-FR is designed as a data platform for future studies evaluating COVID-19 recovery. TRIAL REGISTRATION NUMBER: NCT04602260; Pre-results.

Comprehensive Care Management in Conjunction with Sputum Cytometry-Guided Pharmacotherapy in a Post-Discharge Clinic for Patients with COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are amongst the most common reasons for hospital admission, and recurrent episodes occur frequently. Comprehensive care management (CCM) strategies have modest effect in preventing re-admissions. The objectives of this study were to examine the utility of optimizing anti-inflammatory therapy guided by sputum cytometry in the post-hospitalization setting, and to assess the feasibility and effectiveness of a clinic combining CCM and sputum-guided therapy. This is an observational study examining patients who received open-label CCM and sputum cytometry-guided pharmacotherapy in a COPD post-discharge clinic. Referral was based on high risk for readmission after hospitalization for AECOPD. The primary outcome was the change in COPD-related healthcare utilization before and after Visit 1, and this was analyzed with a mixed-effects negative binomial model controlling for age, number of follow-up clinic visits, pack years, current smoking and FEV1. Of 138 patients referred to the clinic, 73% attended at least one visit. Mean FEV1 was 42.8 (19.3) % predicted. Of the patients attending clinic, 42.6% produced an adequate sputum sample, and 32.7% had an abnormal sputum. By individual, infectious bronchitis was the most common (25.7%), followed by eosinophilic bronchitis (13.9%). Comparing the 6-months prior to and after the first clinic visit, there was a lower incidence rate ratio after visit 1 for COPD-related healthcare utilization (0.26 (95%CI 0.22,0.33; p < 0.001)). A COPD post-discharge clinic combining sputum-guided treatment and CCM was feasible and associated with a nearly 75% reduction in the incidence of COPD-related healthcare utilization.

Pulmonary rehabilitation in interstitial lung diseases.

PURPOSE OF REVIEW: This review will provide an overview of the components and current evidence to support pulmonary rehabilitation in patients with interstitial lung diseases (ILD), focusing on the latest findings in enhancing quality of life and functional capacity using exercise training and education. RECENT FINDINGS: Recent literature demonstrates a longer duration of pulmonary rehabilitation results in sustained improvements in functional capacity and quality of life in patients with ILD. Educational components tailored to ILD provide added value to supervised exercise training. Enhancing exercise training with hyperoxia merits further study and other modalities such as pursed-lip breathing have been shown to be counterproductive. SUMMARY: Recent evidence continues to support the use of tailored pulmonary rehabilitation programs in patients with ILD. Areas which require further investigation include identifying optimal exercise training regimens, educational topics, and breathing techniques that are specifically designed for ILD.

Validity of balance and mobility screening tests for assessing fall risk in COPD.

People with chronic obstructive pulmonary disease (COPD) have balance impairments and an increased risk of falls. The psychometric properties of short balance tests to inform fall risk assessment in COPD are unknown. Our objective was to determine the validity (concurrent, convergent, and known-groups) of short balance and mobility tests for fall risk screening. Participants with COPD aged ≥ 60 years attended a single assessment. Correlation coefficients described the relationships between the Brief Balance Evaluation Systems Test (Brief BESTest), Single-Leg Stance (SLS), Timed Up and Go (TUG), and Timed Up and Go Dual-Task (TUG-DT) tests, with the comprehensive Berg Balance Scale (BBS), chair-stand test, and measures of exercise tolerance, functional limitation, disability, and prognosis. Independent t-tests or Mann-Whitney U tests were used to examine differences between groups with respect to fall risk. Receiver operating characteristic curves examined the ability of the screening tests to identify individuals with previous falls. A total of 86 patients with COPD completed the study (72.9 ± 6.8 years; forced expiratory volume in 1 second: 47.3 ± 20.3% predicted). The Brief BESTest identified individuals who reported a previous fall (area under the curve (AUC) = 0.715, p = 0.001), and the SLS showed borderline acceptable accuracy in identifying individuals with a fall history (AUC = 0.684, p = 0.004). The strongest correlations were found for the Brief BESTest and SLS with the BBS (r = 0.80 and r = 0.72, respectively) and between the TUG and TUG-DT with the chair-stands test (r = 0.73 and r = 0.70, respectively). The Brief BESTest and SLS show the most promise as balance screening tools for fall risk assessment in older adults with COPD. These tests should be further evaluated prospectively.

High Oxygen Delivery to Preserve Exercise Capacity in Patients with Idiopathic Pulmonary Fibrosis Treated with Nintedanib. Methodology of the HOPE-IPF Study.

RATIONALE: Pulmonary rehabilitation improves dyspnea and exercise capacity in idiopathic pulmonary fibrosis (IPF); however, it is unknown whether breathing high amounts of oxygen during exercise training leads to further benefits. OBJECTIVES: Herein, we describe the design of the High Oxygen Delivery to Preserve Exercise Capacity in IPF Patients Treated with Nintedanib study (the HOPE-IPF study). The primary objective of this study is to determine the physiological and perceptual impact of breathing high levels of oxygen during exercise training in patients with IPF who are receiving antifibrotic therapy. METHODS: HOPE-IPF is a two-arm double-blind multicenter randomized placebo-controlled trial of 88 patients with IPF treated with nintedanib. Patients will undergo 8 weeks of three times weekly aerobic cycle exercise training, breathing a hyperoxic gas mixture with a constant fraction of 60% inhaled oxygen, or breathing up to 40% oxygen as required to maintain an oxygen saturation level of at least 88%. MEASUREMENTS AND MAIN RESULTS: End points will be assessed at baseline, postintervention (Week 8), and follow-up (Week 26). The primary analysis will compare the between-group baseline with post-training change in endurance time during constant work rate cycle exercise tests. Additional analyses will evaluate the impact of training with high oxygen delivery on 6-minute walk distance, dyspnea, physical activity, and quality of life. CONCLUSIONS: The HOPE-IPF study will lead to a comprehensive understanding of IPF exercise physiology, with the potential to change clinical practice by indicating the need for increased delivery of supplemental oxygen during pulmonary rehabilitation in patients with IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02551068).

Physiologic characterization of the chronic bronchitis phenotype in GOLD grade IB COPD.

BACKGROUND: Smokers with persistent cough and sputum production (chronic bronchitis [CB]) represent a distinct clinical phenotype, consistently linked to negative clinical outcomes. However, the mechanistic link between physiologic impairment, dyspnea, and exercise intolerance in CB has not been studied, particularly in those with mild airway obstruction. We, therefore, compared physiologic abnormalities during rest and exercise in CB to those in patients without symptoms of mucus hypersecretion (non-CB) but with similar mild airway obstruction. METHODS: Twenty patients with CB (≥ 3 months cough/sputum in 2 successive years), 20 patients without CB but with GOLD (Global Initiative for Chronic Obstructive Lung Disease) grade IB COPD, and 20 age- and sex-matched healthy control subjects underwent detailed physiologic testing, including tests of small airway function and a symptom-limited incremental cycle exercise test. RESULTS: Patients with CB (mean ± SD postbronchodilator FEV1, 93% ± 12% predicted) had greater chronic activity-related dyspnea, poorer health-related quality of life, and reduced habitual physical activity compared with patients without CB and control subjects (all P < .05). The degree of peripheral airway dysfunction and pulmonary gas trapping was comparable in both patient groups. Peak oxygen uptake was similarly reduced in patients with CB and those without compared with control subjects (% predicted ± SD, 70 ± 26, 71 ± 29 and 106 ± 43, respectively), but those with CB had higher exertional dyspnea ratings and greater respiratory mechanical constraints at a standardized work rate than patients without CB (P < .05). CONCLUSIONS: Patients with CB reported greater chronic dyspnea and activity restriction than patients without CB and with similar mild airway obstruction. The CB group had greater dynamic respiratory mechanical impairment and dyspnea during exercise than patients without CB, which may help explain some differences in important patient-centered outcomes between the groups.

Mechanisms of exercise intolerance in global initiative for chronic obstructive lung disease grade 1 COPD.

The purpose of this study was to determine if a dissociation existed between respiratory drive, as estimated by diaphragmatic electromyography (EMGdi), and its pressure-generating capacity during exercise in mild chronic obstructive pulmonary disease (COPD) and whether this, if present, had negative sensory consequences. Subjects meeting spirometric criteria for mild COPD (n=16) and age and sex-matched controls (n=16) underwent detailed pulmonary function testing and a symptom limited cycle test while detailed ventilatory, sensory and respiratory mechanical responses were measured. Compared with controls, subjects with mild COPD had greater ventilatory requirements throughout submaximal exercise. At the highest equivalent work rate of 60 W, they had a significantly higher: total work of breathing (32±17 versus 16±7 J·min(-1); p<0.01); EMGdi (37.3±17.3 versus 17.9±11.7% of maximum; p<0.001); and EMGdi to transdiaphragmatic pressure ratio (0.87±0.38 versus 0.52±0.27; p<0.01). Dyspnoea-ventilation slopes were significantly higher in mild COPD than controls (0.17±0.12 versus 0.10±0.05; p<0.05). However, absolute dyspnoea ratings reached significant levels only at high levels of ventilation. Increased respiratory effort and work of breathing, and a wider dissociation between diaphragmatic activation and pressure-generating capacity were found at standardised work rates in subjects with mild COPD compared with controls. Despite these mechanical and neuromuscular abnormalities, significant dyspnoea was only experienced at higher work rates.

Emerging concepts and therapies for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Although considerable advances have been made in the diagnosis and treatment of COPD, much remains to be done both to alleviate symptoms and reduce mortality associated with this condition. Previously, diagnosis, management, and research all centred on staging based on the forced expiratory flow in 1 second. It is now becoming apparent that this is inadequate to truly capture current disease burden and future deterioration. Fortunately, new approaches to care are constantly being identified. It is now known that symptoms and, in particular, exacerbations represent pivotal events in the patient's life that should trigger optimization of care. Much work is currently underway to identify various phenotypes in COPD because it has become obvious that this is a heterogeneous disease and applying the same management algorithms for all patients is insufficient. Several new medications are at various stages of development, some being approved and on the market, while others are undergoing clinical trials. These allow for more options for individualized care of patients. In addition, new applications of old medications, such as long­term antibiotics, also provide new options for patients struggling with recurrent symptoms. Finally, the growing awareness that this is a heterogeneous disease composed not only of differing phenotypes but also having significant extrapulmonary comorbidities have opened new avenues of research and interdisciplinary collaboration that will further enable us to offer personalized care to patients.

Does the respiratory system limit exercise in mild chronic obstructive pulmonary disease?

RATIONALE: It is not known if abnormal dynamic respiratory mechanics actually limit exercise in patients with mild chronic obstructive pulmonary disease (COPD). We reasoned that failure to increase peak ventilation and Vt in response to dead space (DS) loading during exercise would indicate true ventilatory limitation to exercise in mild COPD. OBJECTIVES: To compare the effects of DS loading during exercise on ventilation, breathing pattern, operating lung volumes, and dyspnea intensity in subjects with mild symptomatic COPD and age- and sex-matched healthy control subjects. METHODS: Twenty subjects with Global Initiative for Chronic Obstructive Lung Disease stage I COPD and 20 healthy subjects completed two symptom-limited incremental cycle exercise tests, in randomized order: unloaded control and added DS of 0.6 L. MEASUREMENTS AND MAIN RESULTS: Peak oxygen uptake and ventilation were significantly lower in COPD than in health by 36% and 41%, respectively. With added DS compared with control, both groups had small decreases in peak work rate and no significant increase in peak ventilation. In health, peak Vt and end-inspiratory lung volume increased significantly with DS. In contrast, the COPD group failed to increase peak end-inspiratory lung volume and had a significantly smaller increase in peak Vt during DS. At 60 W, a 50% smaller increase in Vt (P < 0.001) in response to added DS in COPD compared with health was associated with a greater increase in dyspnea intensity (P = 0.0005). CONCLUSIONS: These results show that the respiratory system reached or approached its physiologic limit in mild COPD at a lower peak work rate and ventilation than in healthy participants. Clinical trial registered with www.clinicaltrials.gov (NCT 00975403).

Components of the COPD Assessment Test (CAT) associated with a diagnosis of COPD in a random population sample.

The aim of this study was to determine if components of the COPD Assessment Test (CAT), a validated health status impairment instrument, had additional utility in identifying patients at risk for COPD in whom spirometry testing is appropriate. This study was part of the Canadian Obstructive Lung Disease prevalence study. Consenting participants ≥ 40 years of age were identified by random digit dialing. Smoking history, 8-item CAT scores, and post-bronchodilator spirometry were recorded for each. Stepwise logistic regression analysis was used to identify variables related to the presence of airway obstruction and a final logistic model was developed which best predicted COPD in this sample. Of the 801 individuals approached, 532 were included: 51 (9.6%) had COPD, the majority (92%) of whom fit GOLD I or II severity criteria. Items that correlated significantly with a COPD diagnosis included the CAT total score (p = 0.01) and its breathlessness (p < 0.0001) and phlegm (p = 0.001) components. The final logistic model included: age (<55 or ≥55 years), smoking status (current, former, never) and the CAT breathlessness score (ordinal scale 0-5). The area under the receiver-operating characteristic curve for this model was 0.77, sensitivity was 77.6%, specificity was 64.9% and the positive likelihood ratio was 2.21. In summary, the triad of smoking history, age at least 55 years and the presence of exertional breathlessness were key elements of a simple model which had reliable measurement properties when tested in a random population. This may help identify patients at risk for COPD for whom spirometry testing is recommended.

Severe bronchorrhea in a patient with bronchioloalveolar carcinoma.

Mucinous bronchioloalveolar carcinoma (BAC) can be associated with significant bronchorrhea. A 46-year-old man presented with BAC with 2,000 mL of sputum production on a daily basis, which prevented him from being extubated. As this condition is rare, there are only case reports outlining the therapy for the associated bronchorrhea. We used azithromycin, scopolamine, and inhaled fluticasone with moderate success. The initiation of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, resulted in dramatic improvement in the volume of pulmonary secretions produced. The patient's EGFR mutation status was subsequently found to be negative, which supports the hypothesis that the mechanism of reduction of bronchorrhea is independent of the antiproliferative effect of the drug.

Effect of adjunct fluticasone propionate on airway physiology during rest and exercise in COPD.

RATIONALE: Combination therapy with corticosteroid and long-acting ß(2)-agonists (LABA) in a single inhaler is associated with superior effects on airway function and exercise performance in COPD compared with LABA monotherapy. The physiological effects of adding inhaled corticosteroid monotherapy to maintenance bronchodilator therapy (long-acting anticholinergics and LABA singly or in combination) in COPD are unknown. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study (NCT00387036) to compare the effects of inhaled fluticasone propionate 500 µg (FP500) twice-daily and placebo (PLA) on airway function during rest and exercise, measured during constant work rate cycle exercise at 75% of maximum incremental cycle work rate, in 17 patients with COPD (FEV(1) ≤ 70% predicted). RESULTS: After treatment with FP500 compared to PLA, there were significant increases in post-dose measurements of FEV(1) (+115 mL, P = 0.006) and the FEV(1)/FVC ratio (+2.5%, P = 0.017), along with decreases in plethysmographic residual volume (-0.32L; P = 0.031), functional residual capacity (-0.30L, P = 0.033), and total lung capacity (-0.30L, P = 0.027) but no changes in vital capacity or inspiratory capacity (IC). Post-treatment comparisons demonstrated a significant improvement in endurance time by 188 ± 362 s with FP500 (P = 0.047) with no concomitant increase in dyspnea intensity. End-inspiratory and end-expiratory lung volumes were reduced at rest and throughout exercise with FP500 compared with PLA (P < 0.05). CONCLUSION: Inhaled FP500 monotherapy was associated with consistent and clinically important improvements in FEV(1), static lung volumes, dynamic operating lung volumes, and exercise endurance when added to established maintenance long-acting bronchodilator therapy in patients with moderate to severe COPD.

Recent advances in pharmacotherapy for dyspnea in COPD.

Dyspnea is the most distressing symptom experienced by those suffering from advanced stages of chronic obstructive pulmonary disease (COPD). Activity-related dyspnea in COPD is multifactorial but is associated with increased central neural drive, impaired dynamic respiratory mechanics and abnormal respiratory muscle function. Each of these components can potentially be targeted for pharmacotherapy. Recent advances in the pharmacotherapy of COPD include the development of new long-acting bronchodilators which, when combined, provide sustained improvements in dyspnea. Additionally, novel applications of older therapies such as opiates, furosemide, helium-oxygen, and statins show early promise as dyspnea-relieving interventions in COPD. Effective pharmacological manipulation of the affective dimension of dyspnea remains an important challenge. In this review of the recent literature in this field, we highlight the main advances that have been achieved.

Sex differences in exertional dyspnea in patients with mild COPD: physiological mechanisms.

The purpose of this study was to evaluate the physiological basis for sex-differences in exercise-induced dyspnea in patients with mild COPD. We compared operating lung volumes, breathing pattern and dyspnea during incremental cycling in 32 men (FEV(1)=86±10% predicted) and women (FEV(1)=86±12% predicted) with mild COPD and 32 age-matched controls. There were no sex differences in dyspnea in the control group at any work-rate or ventilation (V(E)). Women with COPD had significantly greater dyspnea than men at 60 and 80 W. At 80 W, dyspnea ratings were 5.7±2.3 and 3.3±2.5 Borg units (P<0.05) and the V(E) to maximal ventilatory capacity ratio was 72% and 55% in women and men, respectively (P<0.05). Comparable increases in dynamic hyperinflation were seen in both male and female COPD groups at symptom limitation but women reached tidal volume constraints at a lower work rate and V(E) than men. Superimposing mild COPD on the normal aging effects had greater sensory consequences in women because of their naturally reduced ventilatory reserve.

The role of pharmacotherapy in mild to moderate chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and most of those afflicted have mild to moderate disease as measured by spirometry. There is mounting evidence that even mild airway obstruction is associated with activity-related dyspnea, exercise limitation, impaired quality of life, increased hospitalization and mortality. As our understanding of the complex, heterogeneous pathophysiology and clinical consequences of milder COPD continues to grow, there is increasing interest in the potential impact of therapeutic interventions beyond smoking cessation. Unfortunately, few clinical trials have included patients with mild to moderate disease and the evidence base for pharmacological treatment in this subpopulation is currently lacking. Recent short-term mechanistic studies confirm that reversal of airway smooth muscle cholinergic tone consistently improves respiratory mechanics during rest and exercise in mild COPD but long-term clinical benefits remain to be evaluated. Secondary analysis of large, prospective studies designed to evaluate the efficacy of long-acting bronchodilators, inhaled corticosteroids and combination therapy indicate that patients with moderate COPD achieve comparable benefits to those with advanced disease. In the absence of evidence-based guidelines for the management of milder COPD, treatment choices are driven mainly by clinical presentation: for those with persistent and troublesome activity-related dyspnea a trial of inhaled bronchodilator therapy is justified; for those with a propensity for recurrent infective exacerbations, consideration of additional anti-inflammatory treatment seems reasonable. In this paper, we review the current knowledge base and emerging paradigm for the pharmacological treatment of mild to moderate COPD.