Exercise responses and mental health symptoms in COVID-19 survivors with dyspnoea.

Objectives: Dyspnoea is a common persistent symptom post-coronavirus disease 2019 (COVID-19) illness. However, the mechanisms underlying dyspnoea in the post-COVID-19 syndrome remain unclear. The aim of our study was to examine dyspnoea quality and intensity, burden of mental health symptoms, and differences in exercise responses in people with and without persistent dyspnoea following COVID-19. Methods: 49 participants with mild-to-critical COVID-19 were included in this cross-sectional study 4 months after acute illness. Between-group comparisons were made in those with and without persistent dyspnoea (defined as modified Medical Research Council dyspnoea score ≥1). Participants completed standardised dyspnoea and mental health symptom questionnaires, pulmonary function tests, and incremental cardiopulmonary exercise testing. Results: Exertional dyspnoea intensity and unpleasantness were increased in the dyspnoea group. The dyspnoea group described dyspnoea qualities of suffocating and tightness at peak exercise (p<0.05). Ventilatory equivalent for carbon dioxide (V'E/V'CO2) nadir was higher (32±5 versus 28±3, p<0.001) and anaerobic threshold was lower (41±12 versus 49±11% predicted maximum oxygen uptake, p=0.04) in the dyspnoea group, indicating ventilatory inefficiency and deconditioning in this group. The dyspnoea group experienced greater symptoms of anxiety, depression and post-traumatic stress (all p<0.05). A subset of participants demonstrated gas-exchange and breathing pattern abnormalities suggestive of dysfunctional breathing. Conclusions: People with persistent dyspnoea following COVID-19 experience a specific dyspnoea quality phenotype. Dyspnoea post-COVID-19 is related to abnormal pulmonary gas exchange and deconditioning and is linked to increased symptoms of anxiety, depression and post-traumatic stress.

Pulmonary sequelae of SARS-CoV-2 infection and factors associated with persistent abnormal lung function at six months after infection: Prospective cohort study.

BACKGROUND: Information on the long-term pulmonary sequelae following SARS-CoV-2 infection is limited. METHODS: Prospective cohort study of hospitalized and non-hospitalized adult patients age >18 with documented SARS-CoV-2 infection by RT-PCR three months prior to enrolment between June and December 2020. Participants underwent full pulmonary function test (PFT), cardiopulmonary exercise testing at 3 months and 6 months. Primary outcome was mean differences of forced vital capacity (FVC), diffuse capacity of lung for carbon monoxide (DLCO), and oxygen consumption (VO2) at 6 vs. 3 months. Secondary outcomes were respiratory outcomes classified into 5 clinical groups-no lung disease, resolved lung disease, persistent lung disease, PFT abnormalities attributable to pre-existing lung disease or other factors, and mild PFT abnormalities of uncertain clinical significance. RESULTS: Fifty-one, 30 hospitalized and 21 non-hospitalized, participants were included. Median age was 51 years; 20 (39.2%) were female. Mean (±SD) percent predicted values of FVC, DLCO and VO2 at 3 vs 6-month-visits were 96.2 ± 15.6 vs. 97.6 ± 15.5, 73.74 ±18 vs. 78.5 ± 15.5, and 75.5 ± 18.9 vs. 76.1 ± 21.5, respectively. Nineteen (37%) patients had physiologic and/or radiographic evidence of lung disease at 3 months with eight (15.7%) continuing to have persistent disease at 6 months. History of diabetes, hypertension, ICU admission and elevated D-Dimer levels were associated with persistent lung disease at 6 months. INTERPRETATION: Persistent lung disease at 6 months post SARS-CoV-2 infection exists. Changes of lung function between 3- and 6-months are not significant. A longer follow-up is required to determine long-term prognosis.

Cardiorespiratory physiology, exertional symptoms, and psychological burden in post-COVID-19 fatigue.

Fatigue is a common, debilitating, and poorly understood symptom post-COVID-19. We sought to better characterize differences in those with and without post-COVID-19 fatigue using cardiopulmonary exercise testing. Despite elevated dyspnoea intensity ratings, V̇O2peak (ml/kg/min) was the only significant difference in the physiological responses to exercise (19.9 ± 7.1 fatigue vs. 24.4 ± 6.7 ml/kg/min non-fatigue, p = 0.04). Consistent with previous findings, we also observed a higher psychological burden in those with fatigue in the context of similar resting cardiopulmonary function. Our findings suggest that lower cardiorespiratory fitness and/or psychological factors may contribute to post-COVID-19 fatigue symptomology. Further research is needed for rehabilitation and symptom management following SARS-CoV-2 infection.

The Impact of Multidisciplinary Discussion (MDD) in the Diagnosis and Management of Fibrotic Interstitial Lung Diseases.

Accurate diagnosis of interstitial lung disease (ILD) is crucial for management and prognosis but can be challenging even for experienced clinicians. Expert multidisciplinary discussion (MDD) is considered the reference standard for ILD diagnosis; however, there remain concerns regarding lack of validation studies and relative limited information on the impact of MDD in real-life clinical practice. The goal of this study was to assess the effect of MDD in providing a specific ILD diagnosis, changing the diagnosis provided upon referral, and to determine how often and in which way MDD altered management. Material and Methods. Retrospective observational study in an ILD referral tertiary academic center. MDD diagnoses were categorized as specific, provisional, and unclassifiable ILD. Pre-MDD and MDD diagnoses were compared for change in diagnosis and concordance rates for specific diagnoses. Relevant change in management including initiation or change in pharmacological treatment, referral to surgical biopsy, and nonpharmacological management were recorded. Results. 126 cases were included (79M, 47F, 36-93 years, mean 70 y). Specific MDD diagnosis was provided in 62% (78/126); 12% (15/126) had provisional diagnosis, and 21% (27/126) was unclassifiable. Overall agreement for specific pre-MDD and MDD diagnosis was 41% (52/126) and 80% for idiopathic pulmonary fibrosis (IPF) diagnosis. MDD altered diagnosis in 37% (47/126) and changed management in 39% (50/126). Amongst concordant diagnoses, management was altered in 46% (24/52). In summary, MDD provided a specific diagnosis discordant with pre-MDD diagnosis in a significant proportion of cases and was particularly valuable in the diagnosis of non-IPF ILD. MDD often altered management and had relevant impact on management even in cases with concordant pre-MDD diagnosis.

Development of Learning Curves for Bronchoscopy: Results of a Multicenter Study of Pulmonary Trainees.

BACKGROUND: There are currently no reference standards for the development of competence in bronchoscopy. RESEARCH QUESTION: The aims of this study were to (1) develop learning curves for bronchoscopy skill development and (2) estimate the number of bronchoscopies required to achieve competence. STUDY DESIGN AND METHODS: Trainees from seven North American academic centers were enrolled at the beginning of their pulmonology training. Performance during clinical bronchoscopies was assessed by supervising physicians using the Ontario Bronchoscopy Assessment Tool (OBAT). Group-level learning curves were modeled using a quantile regression growth model, where the dependent variable was the mean OBAT score and the independent variable was the number of bronchoscopies performed at the time the OBAT was completed. RESULTS: A total of 591 OBAT assessments were collected from 31 trainees. The estimated regression quantiles illustrate significantly different learning curves based on trainees' performance percentiles. When competence was defined as the mean OBAT score for all bronchoscopies rated as being completed without need for supervision, the mean OBAT score associated with competence was 4.54 (95% CI, 4.47-4.58). Using this metric, the number of bronchoscopies required to achieve this score varied from seven to 10 for the 90th percentile of trainees and from 109 to 126 for the lowest 10th percentile of trainees. When competence was defined as the mean OBAT score for the first independent bronchoscopy, the mean was 4.40 (95% CI, 4.20-4.60). On the basis of this metric, the number of bronchoscopies required varied from one to 11 for the 90th percentile of trainees and from 83 to 129 for the lowest 10th percentile of trainees. INTERPRETATION: We were able to generate learning curves for bronchoscopy across a range of trainees and centers. Furthermore, we established the average number of bronchoscopies required for the attainment of competence. This information can be used for purposes of curriculum planning and allows a trainee's progress to be compared with an established norm.

Recurrent spontaneous pneumothoraces and bullous emphysema. A novel mutation causing Birt-Hogg-Dube syndrome.

Birt-Hogg-Dube syndrome (BHDS) is a rare form of classically cystic lung disease that may present with spontaneous pneumothorax. The associated skin manifestations (fibrofolliculomas) are not always present. This article describes a case of spontaneous pneumothorax secondary to bullous emphysema in an otherwise healthy gentleman caused by a novel mutation in the folliculin (FLCN) gene.

Development and Validation of a Bronchoscopy Competence Assessment Tool in a Clinical Setting.

RATIONALE: Flexible bronchoscopy is performed by clinicians representing multiple medical specialties in a variety of settings. Given the increasing importance of competency-based assessment in postgraduate training, it is important that this skill be assessed within a competency-based framework using a valid measurement tool. OBJECTIVES: The purpose of this study was to design and validate a practical, competency-based bronchoscopy assessment tool that could be applied to trainees in a clinical setting. METHODS: Focus groups of expert physicians were formed in Ottawa, Canada representing adult medical specialties routinely engaged in preparing trainees to perform flexible bronchoscopy (respiratory medicine, critical care, thoracic surgery and anesthesia). The focus groups were charged with identifying themes and items relevant to the assessment of competency in bronchoscopy. By an iterative process, a bronchoscopy assessment tool was developed, the Ontario Bronchoscopy Assessment Tool (OBAT). The tool was evaluated by first using it to assess learners in a pilot study, refining it based on the results, and then testing the OBAT again in a validation study. MEASUREMENTS AND MAIN RESULTS: The initial tool consisted of 19 items, organized into the following groups: preprocedure planning, sedation and monitoring, technical skill, diagnostic skill, and post-procedure planning. The tool demonstrated high reliability (0.91) and discriminated junior from senior trainees. Based on the results of the pilot, the tool was simplified to a 12-item scale with three subscales: preprocedure planning, technical skills, and post-procedure planning. In the validation study, the assessment tool remained highly reliable (0.92) and discriminated junior from senior trainees with an estimated eight assessments per trainee. CONCLUSIONS: The OBAT demonstrates promise as a reliable tool to assess trainee competence for bronchoscopy in clinical settings.

Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study.

To assess the effect on exercise capacity and tolerability of resveratrol, 13 healthy, sedentary adult volunteers were enrolled in a randomized crossover study comparing resveratrol and placebo over two 4-week periods, with a 2-week time between periods when subjects received no treatment. No significant changes in exercise duration or aerobic capacity (peak oxygen uptake) were observed. Gastrointestinal side effects were more common during resveratrol treatment (77% vs. 15%, p = 0.0048). A small reduction in fasting glucose and small but statistically significant increases in liver enzymes, total cholesterol, and triglycerides were observed, although mean results remained within normal limits. There was no change in complete blood count, inflammatory markers, renal function, or other measures of liver function.

Diffuse pulmonary ossification as a rare cause of interstitial lung disease.

Diffuse pulmonary ossification (DPO) is a rare form of interstitial lung disease. The present article describes a case of DPO in an elderly man who presented with progressive dyspnea on exertion and an isolated reduction in diffusing capacity for carbon monoxide. DPO may occur as sequelae of mitral stenosis, left heart failure, idiopathic pulmonary fibrosis, recurrent aspiration pneumonia, solid organ transplant, adult respiratory distress syndrome or may arise idiopathically. In the absence of other findings of interstitial lung disease, a lung biopsy is unlikely to be helpful in the management of these patients.

Physiology and clinical applications of cardiopulmonary exercise testing in lung cancer surgery.

Cardiopulmonary exercise testing (CPET) permits measurement of oxygen uptake (Vo2), an indicator of overall cardiopulmonary fitness and a useful measurement in the assessment of operative risk for lung cancer patients. The evidence supporting the use of CPET in pre-operative assessment of the lung cancer surgery patient is examined. CPET methodology and limitations, as well as alternatives to CPET for risk assessment are discussed.

Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study.

BACKGROUND: Many patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results. METHODS: We performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy. RESULTS: Analyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: -17.3-69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77-21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups. CONCLUSIONS: Our study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration.

Pulmonary actinomycosis in a male patient with a tracheal bronchus.

BACKGROUND: Tracheal bronchus is a congenital malformation comprising an abnormal bronchus originating from the trachea or other bronchus. This malformation has been associated with recurrent pneumonia in children, but is rarely associated with infection in adults. Actinomyces species are rare causes of necrotizing pneumonias that often masquerade as malignancy, lung abscesses and tuberculosis. METHODS AND RESULTS: A case involving a 46-year-old man with a tracheal bronchus and chronic pneumonia syndrome is presented. Bronchialveolar lavage and transthoracic needle biopsy demonstrated the presence of Actinomyces meyeri and Fusobacterium species. CONCLUSIONS: The present article reports the first documented case of actinomycosis occurring in a patient with a tracheal bronchus.

Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects.

BACKGROUND AND OBJECTIVE: Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). METHODS: This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. RESULTS: The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. CONCLUSION: Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.

Effects of oxygen on exercise duration in chronic obstructive pulmonary disease patients before and after pulmonary rehabilitation.

BACKGROUND: Supplemental oxygen therapy has been shown to improve exercise performance in patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the magnitude of this benefit would be affected by participation in a pulmonary rehabilitation program. OBJECTIVE: To compare the effects of supplemental oxygen on exercise capacity in nonhypoxemic COPD patients before and after participation in a pulmonary rehabilitation program. METHODS: Sixteen patients with COPD underwent two pairs of constant-load exercise tests before and after participation in a three-month outpatient pulmonary rehabilitation program. Each pair of exercise tests consisted of a test performed with room air and a second test performed with 50% supplemental oxygen, in random order. The primary outcome was the difference in exercise duration between tests performed with supplemental oxygen and with room air. This difference was compared before and after participation in a pulmonary rehabilitation program. RESULTS: Supplemental oxygen therapy improved exercise duration by 75 s before participation in a pulmonary rehabilitation program and by 153 s following pulmonary rehabilitation. Rehabilitation alone improved exercise duration by 28 s, but rehabilitation appeared to augment the exercise benefits of supplemental oxygen therapy by a mean of 78 s (95% CI 11 s to 145 s; P = 0.03). CONCLUSION: The effects of supplemental oxygen therapy were augmented after pulmonary rehabilitation. The improvement in exercise duration with supplemental oxygen following rehabilitation was greater than either supplemental oxygen or pulmonary rehabilitation alone.

Impact of interventional bronchoscopy on quality of life in malignant airway obstruction.

BACKGROUND: Interventional bronchoscopic procedures can re-establish airway patency in the majority of individuals suffering from endobronchial obstruction. However, literature provides limited data on the impact of these procedures on the individual's quality of life (QoL). OBJECTIVES: We evaluated the impact of interventional bronchoscopic procedures aimed at re-establishing airway patency on symptoms and QoL of individuals who do not receive concomitant chemotherapy or radiation therapy. METHODS: Over a 6-month period, we prospectively enrolled patients with symptomatic central airway obstruction related to malignancy and performed laser ablation, cryotherapy, and/or airway stenting in order to re-establish airway patency. QoL was evaluated by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire at one day before, 7 days after, and 1 month after procedure. Dyspnea was also assessed by the Borg scale before the procedure and one day after. RESULTS: Final analysis could be performed on 83% (20/24) of the participants. Improvement in airway diameter was achieved in all patients, and >80% patency was established in 80% (16/20) of the patients. Dyspnea scores had improved in 85% of participants (p = 0.01). Thirteen patients experienced an improvement in QoL, although QoL scores remained stable for the group as a whole. CONCLUSION: Endoscopic procedures can effectively reduce dyspnea associated with malignant central airway obstruction, but this may not always translate into improvements in overall QoL. Administration of QoL questionnaires is feasible, and may help identify domains contributing to patient's decline, and thereby improve overall patient care.

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2008 update - highlights for primary care.

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is preventable and treatable but unfortunately remains underdiagnosed. The purpose of the present article from the Canadian Thoracic Society is to provide up-to-date information so that patients with this condition receive optimal care that is firmly based on scientific evidence. Important summary messages for clinicians are derived from the more detailed Update publication and are highlighted throughout the document. Three key messages contained in the update are: use targeted screening spirometry to establish a diagnosis and initiate prompt management (including smoking cessation) of mild COPD; improve dyspnea and activity limitation in stable COPD using new evidence-based treatment algorithms; and understand the importance of preventing and managing acute exacerbations, particularly in moderate to severe disease.

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update.

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable. Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably. The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence. Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available. The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document. Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations. A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease. The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy. The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition.