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1.
PLoS One ; 16(11): e0260416, 2021.
Article in English | MEDLINE | ID: covidwho-1793553

ABSTRACT

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1-3.2) for breathlessness score 3 and 2.1 (95% CI 1.7-2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4-7.7) for breathlessness score 3 and 3.0 (2.4-3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4-1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2-1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health.


Subject(s)
Lung Diseases/diagnosis , Respiration Disorders/diagnosis , Adolescent , Adult , Asthma/diagnosis , Asthma/epidemiology , Cohort Studies , Cough/diagnosis , Cough/epidemiology , Dyspnea/epidemiology , Female , Forced Expiratory Volume , Humans , Lung Diseases/epidemiology , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Male , Middle Aged , Norway/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Respiration Disorders/epidemiology , Respiratory Sounds , Risk Factors , Young Adult
2.
Heart Lung ; 54: 1-6, 2022.
Article in English | MEDLINE | ID: covidwho-1734427

ABSTRACT

BACKGROUND: Individuals who suffer from coronavirus disease 2019 (COVID-19) pneumonia may experience pulmonary dysfunction during the chronic period due to pulmonary parenchymal damage after acute disease. OBJECTIVES: The aim of the present study was to evaluate the pulmonary function and exercise capacity of patients treated for COVID 19 pneumonia after discharge. METHODS: In this cross-sectional study, 79 people who were hospitalized with COVID-19 between March and October 2020 were evaluated at least two months after discharge. A pulmonary function test and a six-minute walk test were administered to the individuals included in the study. RESULTS: Restrictive-type disorder was detected in 21.5% of the individuals who were evaluated at least two months after discharge. The forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC) values of the pulmonary function tests were significantly lower in the individuals with severe/critical clinical disease compared to those with moderate disease (p = 0.004 and p = 0.001, respectively). Although the six-minute walk test (6MWT) distances were lower in the severe/critical group than in the moderate group, the difference was not statistically significant (p > 0.05). CONCLUSIONS: Individuals who are discharged after hospitalization for COVID-19 pneumonia may develop a restrictive type of pulmonary dysfunction. Therefore, survivors of COVID-19 pneumonia should be evaluated for pulmonary function and rehabilitation needs and should be provided with treatment as required.


Subject(s)
COVID-19 , Pneumonia , COVID-19/complications , Cross-Sectional Studies , Exercise Tolerance , Forced Expiratory Volume , Humans , Lung , Vital Capacity
3.
Int J Environ Res Public Health ; 19(4)2022 02 10.
Article in English | MEDLINE | ID: covidwho-1690248

ABSTRACT

Molecular hydrogen (H2) is potentially a novel therapeutic gas for acute post-coronavirus disease 2019 (COVID-19) patients because it has antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties. The aim of this study was to determine the effect of 14 days of H2 inhalation on the respiratory and physical fitness status of acute post-COVID-19 patients. This randomized, single-blind, placebo-controlled study included 26 males (44 ± 17 years) and 24 females (38 ± 12 years), who performed a 6-min walking test (6 MWT) and pulmonary function test, specifically forced vital capacity (FVC) and expiratory volume in the first second (FEV1). Symptomatic participants were recruited between 21 and 33 days after a positive polymerase chain reaction test. The experiment consisted of H2/placebo inhalation, 2 × 60 min/day for 14 days. Results showed that H2 therapy, compared with placebo, significantly increased 6 MWT distance by 64 ± 39 m, FVC by 0.19 ± 0.24 L, and, in FEV1, by 0.11 ± 0.28 L (all p ≤ 0.025). In conclusion, H2 inhalation had beneficial health effects in terms of improved physical and respiratory function in acute post-COVID-19 patients. Therefore, H2 inhalation may represent a safe, effective approach for accelerating early function restoration in post-COVID-19 patients.


Subject(s)
COVID-19 , Female , Forced Expiratory Volume , Humans , Hydrogen/therapeutic use , Male , Respiratory Function Tests , SARS-CoV-2 , Single-Blind Method
4.
J Med Virol ; 94(5): 2026-2034, 2022 05.
Article in English | MEDLINE | ID: covidwho-1649209

ABSTRACT

In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various postacute signs and symptoms. This study aimed to evaluate patients with postacute COVID-19 over 12 weeks of follow-up. The study included 151 patients who were diagnosed with COVID-19 by real-time polymerase chain reaction of a nasopharyngeal swab 1 month earlier, had radiologic findings consistent with COVID-19 pneumonia, and presented to the post-COVID-19 outpatient clinic between May and August 2021. The patients were divided into three groups based on COVID-19 severity: nonsevere pneumonia (Group 1), severe pneumonia (Group 2), and severe pneumonia requiring intensive care (Group 3). Evaluation of laboratory parameters at 4 and 12 weeks showed that Group 3 had a higher lactose dehydrogenase (LDH) level and a lower mean platelet volume than the other groups at both time points (p = 0.001 for all). Group 3 also had lower percent predicted forced vital capacity (FVC%), percent predicted forced expiration volume in 1 s (FEV1%), and percent predicted diffusion capacity of the lungs for carbon monoxide divided by alveolar volume (DLCO/VA%) compared to Groups 1 and 2 at Week 4 (p = 0.001, 0.004, 0.001, respectively) and compared to Group 1 at 12 weeks (p = 0.002, 0.03, 0.001, respectively). Patients with persistent dyspnea at 12 weeks had significantly lower FEV1%, FVC%, DLCO/VA%, and saturation levels in room air and significantly higher LDH, pro-BNP, D-dimer, and heart rate compared to those without dyspnea (p = 0.001 for all). Although the lungs are most commonly affected after COVID-19 infection, vascular and endothelial damage also causes multisystem involvement. Our study indicates that laboratory values, radiological signs, and pulmonary functional capacity improved in most patients after 12 weeks of follow-up.


Subject(s)
COVID-19 , COVID-19/diagnosis , Follow-Up Studies , Forced Expiratory Volume , Humans , Lung/diagnostic imaging , Respiratory Function Tests
6.
Respir Med ; 191: 106709, 2022 01.
Article in English | MEDLINE | ID: covidwho-1556145

ABSTRACT

INTRODUCTION: Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse. We aim to determine reductions in pulmonary function and respiratory related quality of life up to 12 months after acute COVID-19. METHODS: Patients with acute COVID-19 were enrolled into an ongoing single-centre, prospective observational study and prospectively examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate respiratory limitations. Patients were stratified according to severity of acute COVID-19. RESULTS: Median age of all patients was 57 years, 37.8% were female. Higher age, male sex and higher BMI were associated with acute-COVID-19 severity (p < 0.0001, 0.001 and 0.004 respectively). Also, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity. In patients with restriction and impaired diffusion capacity, FVC improved over 12 months from 61.32 to 71.82, TLC from 68.92 to 76.95, DLCO from 60.18 to 68.98 and KCO from 81.28 to 87.80 (percent predicted values; p = 0.002, 0.045, 0.0002 and 0.0005). The CT-score of lung involvement in the acute phase was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with initially mild disease. CONCLUSION: Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Lung/physiopathology , Quality of Life , Respiratory Insufficiency/physiopathology , Adult , Aged , COVID-19/diagnostic imaging , COVID-19/therapy , Extracorporeal Membrane Oxygenation , Female , Forced Expiratory Volume/physiology , Hospitalization , Humans , Longitudinal Studies , Lung/diagnostic imaging , Male , Middle Aged , Oxygen Inhalation Therapy , Pulmonary Diffusing Capacity/physiology , Recovery of Function , Respiration, Artificial , Respiratory Function Tests , Respiratory Insufficiency/diagnostic imaging , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires , Tomography, X-Ray Computed , Total Lung Capacity/physiology , Vital Capacity/physiology
7.
BMC Pulm Med ; 21(1): 136, 2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1511742

ABSTRACT

BACKGROUND: All over the world, SARS-CoV-2 pneumonia is causing a significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients are still unknown. METHODS: In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. At three months patients underwent radiological and functional follow-up through CT scan, lung function tests, and 6 min walking test. Furthermore, quality of life was assessed through self-reported questionnaires. RESULTS: Among 39 patients with SARS-CoV-2 pneumonia, 32 (82% of all participants) presented abnormalities in CT scan and 25 (64.1%) had lung function tests impairment at three months. Moreover, 31 patients (79.5%) reported a perception of poor health due to respiratory symptoms and all 39 patients showed an overall decreased quality of life. CONCLUSIONS: Medium-term follow up at three months of patients diagnosed with SARS-CoV-2 pneumonia shows the persistence of abnormalities in CT scans, a significant functional impairment assessed by lung function tests and a decreased quality of life in affected patients. Further studies evaluating the long-term impact are warranted to guarantee an appropriate follow-up to patients recovering from SARS-CoV-2 pneumonia.


Subject(s)
COVID-19/physiopathology , Lung/physiopathology , Quality of Life , Aged , COVID-19/diagnostic imaging , Convalescence , Female , Forced Expiratory Volume , Health Status , Humans , Length of Stay , Lung/diagnostic imaging , Male , Middle Aged , Prospective Studies , Pulmonary Diffusing Capacity , Recovery of Function , Respiratory Function Tests , SARS-CoV-2 , Switzerland , Tomography, X-Ray Computed , Vital Capacity , Walk Test
8.
J Med Internet Res ; 23(10): e29218, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1477706

ABSTRACT

BACKGROUND: The COVID-19 pandemic has boosted the use of forced expiratory volume in 1 second (FEV1) telemonitoring in pediatric asthma, but a consensus on its most efficient and effective implementation is still lacking. To find answers, it is important to study how such an intervention is perceived, experienced, and used by both patients and health care professionals (HCPs). OBJECTIVE: The aim of this study was to provide perspectives on how FEV1 home monitoring should be used in pediatric asthma. METHODS: This is a qualitative, multicenter, prospective, observational study which included patients with asthma aged 6-16 and HCPs. Primary outcomes were results of 2 surveys that were sent to all participants at study start and after 3-4 months. Secondary outcomes consisted of FEV1 device usage during 4 months after receiving the FEV1 device. RESULTS: A total of 39 participants (26 patients and 13 HCPs) were included in this study. Survey response rates were 97% (38/39) at the start and 87% (34/39) at the end of the study. Both patients and HCPs were receptive toward online FEV1 home monitoring and found it contributive to asthma control, self-management, and disease perception. The main concerns were about reliability of the FEV1 device and validity of home-performed lung function maneuvers. FEV1 devices were used with a median frequency of 7.5 (IQR 3.3-25.5) during the 4-month study period. CONCLUSIONS: Patients and HCPs are receptive toward online FEV1 home monitoring. Frequency of measurements varied largely among individuals, yet perceived benefits remained similar. This emphasizes that online FEV1 home monitoring strategies should be used as a means to reach individual goals, rather than being a goal on their own.


Subject(s)
COVID-19 , Goals , Child , Forced Expiratory Volume , Humans , Pandemics , Prospective Studies , Reproducibility of Results , SARS-CoV-2
9.
BMC Pulm Med ; 21(1): 326, 2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477411

ABSTRACT

BACKGROUND: Handheld oscillating positive expiratory pressure (OPEP) devices have been a mainstay of treatment for patients with hypersecretory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) since the 1970s. Current devices are reusable and require regular cleaning and disinfection to prevent harbouring potentially pathogenic organisms. Adherence to cleaning regimens for respiratory devices is often poor and in response to this, a prototype disposable OPEP device-the 'UL-OPEP' (University of Limerick-Oscillating Positive Expiratory Pressure device)-was developed to mitigate the risk of contamination by pathogens. The device was previously evaluated successfully in a group of paediatric CF patients. The aim of the current study was to initially evaluate the safety of the prototype in patients with COPD over a period of 1 month to ensure no adverse events, negative impacts on lung function, exercise tolerance, or quality of life. Data on user experience of the device were also collected during post-study follow-up. METHODS: A sample of 50 volunteer participants were recruited from pulmonary rehabilitation clinics within the local hospital network. The patients were clinically stable, productive, and not current or previous users of OPEP devices. Participants were invited to use a prototype disposable OPEP device daily for a period of 1 month. Pre- and post-study lung function was assessed with standard spirometry, and exercise tolerance with the 6-min-walk-test (6MWT). Quality of life was assessed using the St. George's Respiratory Questionnaire (SGRQ), and user experience of the prototype device evaluated using a post-study questionnaire. RESULTS: 24 Participants completed the study: 9 were female. Overall median age was 67.5 years, range 53-85 years. Lung function, 6-min walk test, and SGRQ scores showed no significant change post-study. User feedback was positive overall. CONCLUSIONS: The results indicate that the UL-OPEP is safe to use in patients with COPD. No adverse events were recorded during the study or in the follow-up period of 2 weeks. The device did not negatively impact patients' lung function, exercise tolerance, or quality of life during short term use (1 month), and usability feedback received was generally positive. Larger, longer duration studies will be required to evaluate efficacy. Registration The study was approved as a Clinical Investigation by the Irish Health Products Regulatory Authority (CRN-2209025-CI0085).


Subject(s)
Chest Wall Oscillation/instrumentation , Chest Wall Oscillation/methods , Pulmonary Disease, Chronic Obstructive/therapy , Spirometry/instrumentation , Spirometry/methods , Aged , Aged, 80 and over , Chest Wall Oscillation/psychology , Disposable Equipment , Female , Forced Expiratory Volume , Humans , Ireland , Male , Middle Aged , Patient Satisfaction , Pilot Projects , Spirometry/psychology , Surveys and Questionnaires
10.
BMJ Open ; 11(8): e053446, 2021 08 27.
Article in English | MEDLINE | ID: covidwho-1376513

ABSTRACT

INTRODUCTION: Heart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (ß)-blockers. There is observational evidence that cardioselective ß-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective ß-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective ß-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity. METHODS AND ANALYSES: This is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25-5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40-85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV1) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months. ETHICS AND DISSEMINATION: The study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital. TRIAL REGISTRATION NUMBERS: NCT03917914; CTRI/2020/08/027322.


Subject(s)
Bisoprolol , Pulmonary Disease, Chronic Obstructive , Bisoprolol/therapeutic use , Disease Progression , Double-Blind Method , Forced Expiratory Volume , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic
11.
Respir Res ; 22(1): 237, 2021 Aug 26.
Article in English | MEDLINE | ID: covidwho-1371969

ABSTRACT

Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Respiratory Tract Diseases/physiopathology , Adult , Aged , Female , Finland , Follow-Up Studies , Forced Expiratory Volume , Humans , Length of Stay , Male , Middle Aged , Nitric Oxide/metabolism , Pulmonary Alveoli/metabolism , Respiratory Function Tests , Respiratory Tract Diseases/etiology , Spirometry , Survivors , Vital Capacity
13.
BMJ Open Respir Res ; 8(1)2021 07.
Article in English | MEDLINE | ID: covidwho-1327682

ABSTRACT

INTRODUCTION: The National Health Service for England Long Term Plan identifies respiratory disease as one of its priority workstreams. To assist with earlier and more accurate diagnosis of lung disease they recommend improvement in delivery of quality-assured spirometry. However, there is a likelihood that patients will present with abnormal gas exchange when spirometry results are normal and therefore there will be a proportion of patients whose time to diagnosis is still protracted. We wished to determine the incidence rate of this occurring within our Trust. METHODS: A retrospective review of all patients attending the lung function laboratory for their first pulmonary function assessment from June 2006 to December 2020 was undertaken. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) >-1.64 standardised residual (SR) was used to confirm no obstructive lung function abnormality and FVC >-1.64 SR to confirm no suggestion of a restrictive lung function abnormality. Lung gas transfer for carbon monoxide (TLCO) and transfer coefficient of the lung for carbon monoxide (KCO) <-1.64 SR confirmed the presence of a gas exchange abnormality. Spirometry and gas transfer reference values generated by the Global Lung Initiative were used to determine normality. RESULTS: Of 12 835 eligible first visits with normal FEV1/FVC and FVC, 4856 (37.8%) were identified as having an abnormally low TLCO and 3302 (25.7%) presenting with an abnormally low KCO. Of 3494 with FEV1/FVC SR <-1.64, 3316 also had a ratio of <0.70, meaning 178 (5%) of patients in this cohort would have been misclassified as having obstructive lung disease using the 0.70 cut-off recommended by the Global Initiative for Chronic Obstructive Lung Disease for diagnosing obstructive lung disease. DISCUSSION: In conclusion, to assist with ensuring more accurate and timely diagnosis of lung disease and enhance patients' diagnostic pathway, we recommend the performance of lung gas transfer measurements alongside spirometry in all healthcare settings. To assess and monitor gas transfer at the earliest opportunity we recommend this is implemented into new models being developed within community hubs. This will increase the identification of lung function abnormalities and provide patients with a definitive diagnosis earlier.


Subject(s)
Lung , State Medicine , Forced Expiratory Volume , Humans , Retrospective Studies , Vital Capacity
15.
PLoS One ; 16(6): e0252576, 2021.
Article in English | MEDLINE | ID: covidwho-1256043

ABSTRACT

Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations. It is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD. This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020. Electronic health records were used to determine diagnosis of COPD, ICS use, and clinical outcomes. Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased risk for severe COVID-19 disease. Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative for COVID-19 (p = 0.033). Of those who tested positive for COVID-19 (n = 1288), 371 (28.8%) required hospitalization. In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of ICU admission (36.8% [74/201] vs 31.2% [53/170], p = 0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p = 0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p = 0.80). Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4.02), or mortality (OR: 0.80, CI: 0.43-1.49). In conclusion, ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD followed at the Cleveland Clinic health system. These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/pharmacology , Adrenergic beta-2 Receptor Agonists/adverse effects , Adult , Aged , COVID-19/complications , COVID-19 Testing , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Muscarinic Antagonists/therapeutic use , Nebulizers and Vaporizers , Pandemics , Pulmonary Disease, Chronic Obstructive/complications , Registries , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
16.
Respir Res ; 22(1): 164, 2021 May 29.
Article in English | MEDLINE | ID: covidwho-1247590

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection. METHODS: We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects. RESULTS: ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = - 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of -0.26 (p = 0.033) and - 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES. Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E-06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively). CONCLUSION: This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.


Subject(s)
COVID-19/genetics , Lung/metabolism , Pulmonary Disease, Chronic Obstructive/genetics , Transcriptome , Aged , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Basigin/genetics , Basigin/metabolism , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/physiopathology , Case-Control Studies , Female , Forced Expiratory Volume , Gene Expression Regulation , Humans , Lung/physiopathology , Male , Middle Aged , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/physiopathology , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/genetics , Receptor, Angiotensin, Type 2/metabolism , Vital Capacity
17.
Respir Med ; 184: 106470, 2021 08.
Article in English | MEDLINE | ID: covidwho-1230755

ABSTRACT

Patients recovering from coronavirus disease 2019 (COVID-19) may not return to a pre-COVID functional status and baseline levels of healthcare needs after discharge from acute care hospitals. Since the long-term outcomes of COVID-19 can be more severe in patients with underlying cardiorespiratory diseases, we aimed at verifying the impact of a preexisting cardiorespiratory comorbidity on multidisciplinary rehabilitation in post-COVID-19 patients. We enrolled 95 consecutive patients referring to the Pulmonary Rehabilitation Unit of Istituti Clinici Scientifici Maugeri Spa SB, IRCCS of Telese Terme, Benevento, Italy after being discharged from the COVID-19 acute care ward and after recovering from acute COVID-19 pneumonia. Forty-nine of them were not suffering from underlying comorbidities, while 46 had a preexisting cardiorespiratory disease. Rehabilitation induced statistically significant improvements in respiratory function, blood gases and the ability to exercise both in patients without any preexisting comorbidities and in those with an underlying cardiorespiratory disease. Response to the rehabilitation cycle tended to be greater in those without preexisting comorbidities, but DLco%-predicted was the only parameter that showed a significant greater improvement when compared to the response in the group of patients with underlying cardiorespiratory comorbidity. This study suggests that multidisciplinary rehabilitation may be useful in post-COVID-19 patients regardless of the presence of preexisting cardiorespiratory comorbidities.


Subject(s)
COVID-19/rehabilitation , Interdisciplinary Communication , Patient Care Team , Rehabilitation/methods , COVID-19/epidemiology , COVID-19/physiopathology , Carbon Monoxide/blood , Cardiovascular Diseases/epidemiology , Comorbidity , Female , Forced Expiratory Volume , Humans , Italy/epidemiology , Lung/physiopathology , Male , Middle Aged , Recovery of Function , Respiratory Tract Diseases/epidemiology , Treatment Outcome , Vital Capacity , Walk Test
18.
Respir Med ; 184: 106435, 2021 08.
Article in English | MEDLINE | ID: covidwho-1230751

ABSTRACT

INTRODUCTION: Lung function in survivors of SARS-Co-V2 pneumonia is poorly known, but concern over the possibility of sequelae exists. METHODS: Retrospective study on survivors with confirmed infection and pneumonia on chest-CT. Correlations between PFT and residual radiologic anomalies at three months taking into account initial clinical and radiological severity and steroid use during acute phase. RESULTS: 137 patients (69 men, median age 59 (Q1 50; Q3 68), BMI 27.5 kg/m2 (25.1; 31.7)) were assessed. Only 32.9% had normal PFT, 75 had altered DLCO. Median (Q1; Q3) values were: VC 79 (66; 92) % pred, FEV1 81 (68; 89), TLC 78 (67; 85), DLCO 60 (44; 72), and KCO 89 (77; 105). Ground glass opacities (GGO) were present in 103 patients (75%), reticulations in 42 (30%), and fibrosis in 18 (13%). There were significantly lower FEV1 (p = 0.0089), FVC (p = 0.0010), TLC (p < 0.0001) and DLCO (p < 0.0001) for patients with GGO, lower TLC (p = 0.0913) and DLCO (p = 0.0181) between patients with reticulations and lower FVC (p = 0.0618), TLC (p = 0.0742) DLCO (p = 0.002) and KCO (p = 0.0114) between patients with fibrosis. Patients with initial ≥50% lung involvement had significantly lower FEV1 (p = 0.0019), FVC (p = 0.0033), TLC (p = 0.0028) and DLCO (p = 0.0003) compared to patients with ≤10%. There was no difference in PFT and residual CT lesions between patients who received steroids and those who did not. CONCLUSION: The majority of patients have altered PFT at three months, even in patients with mild initial disease, with significantly lower function in patients with residual CT lesions. Steroids do not seem to modify functional and radiological recovery. Long-term follow-up is needed.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/physiopathology , Forced Expiratory Volume , Lung/diagnostic imaging , Vital Capacity , Female , Humans , Lung/physiopathology , Male , Middle Aged , Radiography, Thoracic , Respiratory Function Tests , Retrospective Studies , Severity of Illness Index , Time Factors , Tomography, X-Ray Computed
19.
Respiration ; 100(7): 594-599, 2021.
Article in English | MEDLINE | ID: covidwho-1194385

ABSTRACT

BACKGROUND AND OBJECTIVES: The 6-minute walk test (6MWT), as a clinical assessment tool for functional exercise capacity, is an integral component of lung allocation scores (LASs). In times of the coronavirus disease (COVID-19) pandemic, patients underwent 6MWTs wearing a surgical mask in ambulatory care. We investigated the impact of wearing a mask on 6-minute walk distances (6MWDs). METHOD: 6MWDs of 64 patients with end-stage lung diseases wearing an oronasal surgical mask were retrospectively compared to previously investigated 6MWDs of the same cohort, in a pre-COVID-19 pandemic era, without wearing a mask. Four patients were excluded due to a primary vascular disease, 29 patients due to clinically unstable pulmonary functions, and 1 patient due to a psychiatric disorder. RESULTS: The median age of the patients included was 55 (46-58) years; 15 (48%) were male. Ten (32.2%) were on the Eurotransplant lung transplant waiting list with a median LAS of 34.3 (31.9-36.2). Twenty (64.5%) patients had chronic obstructive pulmonary diseases, 7 (22.6%) had interstitial lung diseases, and 4 (12.9%) had other end-stage lung diseases. The mean 6MWD without versus with wearing a mask was 306.9 (101.9) versus 305.7 (103.8) m, with a mean difference of -1.19 m (95% confidence interval -13.4 to 11.03). The observed difference is statistically equivalent to zero (p < 0.001). No significant differences in 6MWDs were observed between the clinical groups. CONCLUSION: Wearing an oronasal surgical mask did not affect the 6MWDs of patients with advanced lung diseases. Therefore, a masked 6MWT appears to provide a reliable examination of functional exercise capacity in this cohort.


Subject(s)
COVID-19/prevention & control , Lung Diseases, Interstitial/physiopathology , Masks , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Insufficiency/physiopathology , Walk Test/methods , Blood Gas Analysis , Chronic Disease , Exercise Tolerance , Female , Forced Expiratory Volume , Humans , Lung Diseases/physiopathology , Lung Diseases/surgery , Lung Diseases, Interstitial/surgery , Lung Transplantation , Male , Middle Aged , Minimal Clinically Important Difference , Plethysmography, Whole Body , Pulmonary Disease, Chronic Obstructive/surgery , Reproducibility of Results , Respiratory Insufficiency/surgery , Retrospective Studies , SARS-CoV-2 , Vital Capacity
20.
Int J Tuberc Lung Dis ; 25(4): 262-270, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1190586

ABSTRACT

BACKGROUND: Persistent respiratory symptoms and lung function deficits are common after patients with TB. We aimed to define the burden of post-TB lung disease (PTLD) and assess associations between symptoms and impairment in two high TB incidence communities.METHODS: This was a cross-sectional survey of adults in Cape Town, South Africa who completed TB treatment 1-5 years previously. Questionnaires, spirometry and 6-minute walking distance (6MWD) were used to assess relationships between outcome measures and associated factors.RESULTS: Of the 145 participants recruited (mean age: 42 years, range: 18-75; 55 [38%] women), 55 (38%) had airflow obstruction and 84 (58%) had low forced vital capacity (FVC); the mean 6MWD was 463 m (range: 240-723). Respiratory symptoms were common: chronic cough (n = 27, 19%), wheeze (n = 61, 42%) and dyspnoea (modified MRC dyspnoea score 3 or 4: n = 36, 25%). There was poor correlation between FVC or obstruction and 6MWD. Only low body mass index showed consistent association with outcomes on multivariable analyses. Only 19 (13%) participants had a diagnosis of respiratory disease, and 16 (11%) currently received inhalers.CONCLUSION: There was substantial burden of symptoms and physiological impairment in this "cured" population, but poor correlation between objective outcome measures, highlighting deficits in our understanding of PTLD.


Subject(s)
Lung , Pulmonary Disease, Chronic Obstructive , Adult , Cross-Sectional Studies , Female , Forced Expiratory Volume , Humans , South Africa/epidemiology , Spirometry , Vital Capacity
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