Effects of Daily Physical Activity on Exercise Capacity in Chronic Obstructive Pulmonary Disease.

Background and Objectives: In adults, 150 to 300 min a week of moderate-intensity physical activity is the recommended daily level to maintain or improve fitness. In subjects with chronic obstructive pulmonary disease (COPD), reductions in daily physical activity (DPA) amounts are related to clinically significant outcomes. In this study, we ascertain whether or not COPD patients, when clustered into active (DPA ≥ 30 min a day, 5 days a week) and inactive (DPA < 30 min a day, 5 days a week), may differ in exercise capacity, as assessed by a cardiopulmonary exercise test (CPET). Materials and Methods: A large sample of clinically stable COPD patients was retrospectively recruited and then underwent spirometry and an incremental ramp protocol 5-15 watts/min CPET. DPA was assessed by a questionnaire. Results: A total of 83 (female 25%, age range 41-85 y) active and 131 (female 31%, age range 49-83 y) inactive participants were enrolled. They were similar in age, sex distribution, body mass index (BMI) and in spirometry. The two groups were significantly different in dyspnea on exertion, as assessed by the modified Medical Research Council (mMRC), and in cardio-metabolic parameters, but not in ventilatory ones, as confirmed by the CPET. Conclusions: COPD patients experiencing physical activity of at least 30 min a day, 5 days a week, showed a greater exercise capacity and an improved cardiovascular response to exercise, when compared to inactive ones. Active and inactive participants did not differ in terms of airflow obstruction severity as well as in dynamic hyperinflation and ventilatory inefficiency during exercise. This study further suggests the benefits of regular physical activity in COPD.

Detection of Small Airway Dysfunction in Asthmatic Patients by Spirometry and Impulse Oscillometry System.

BACKGROUND: There is no gold standard in diagnosing SAD. Indicators of SAD are considered: (a) a value <65% of predicted values of two of three measures, FEF25-75, FEF50 e FEF75 (FEF+); (b) a value of FEV3/FEV6 < LLN (FEV3/FEV6+); (c) an IOS value of R5-R20 >0.07 kPa·s·L-1 (R5-R20+). AIM AND OBJECTIVES: The aim of the study was to ascertain, in asthmatic patients, whether spirometry and IOS indicators agree in detecting SAD. We also assessed the relationship between spirometry and IOS indicators and clinical features of asthma. METHODS: We prospectively recruited adult asthmatic patients. Anthropometric and clinical characteristics were recorded. All patients performed spirometry and IOS tests. RESULTS: We enrolled 301 asthmatic patients (179 females; mean age 50 ± 16 years) with normal to moderately severe degree of airway obstruction; 91% were non-smokers, 74% were atopic, 28% had an exacerbation in the previous year, and 18% had a poor asthma control by ACT. SAD was diagnosed in 62% of patients through FEF+, in 40% through FEV3/FEV6+ and in 41% through R5-R20+. κ values were 0.49 between FEF+ and FEV3/FEV6+, 0.20 between FEF+ and R5-R20+, 0.07 between FEV3/FEV6+ and R5-R20+. R5-R20+ but not FEF+ and FEV3/FEV6+ was significantly associated with ACT score (p < 0.05). CONCLUSIONS: Our study shows that in mild to moderately severe asthmatic patients, spirometry and IOS indicators are complementary in diagnosing SAD. Additionally, IOS indicator, but not spirometry ones, was related to asthma control.

Small Airways: Not Just Air Ducts - Pathophysiological Aspects and Clinical Implications.

The airways smaller than 2 mm diameter are named small airways. They are essential for the transport and exchange of oxygen and carbon dioxide and at the same time play a relevant role in pulmonary mechanics, contributing to the subdivision of lung volumes. Measurement of small airway function is, therefore, crucial in patients with respiratory disease. This overview focuses on the physiological aspects of the small airways, considered as air ducts as well as determinants of pulmonary mechanics, the most common tools for evaluating their function and treatment implications.

Coronavirus Disease 2019: COSeSco - A Risk Assessment Score to Predict the Risk of Pulmonary Sequelae in COVID-19 Patients.

BACKGROUND: The presence of interstitial pneumonia in coronavirus disease 2019 (COVID-19) patients, as diagnosed through laboratory, functional, and radiological data, provides potential predicting factors of pulmonary sequelae. OBJECTIVES: The objectives were the creation of a risk assessment score for pulmonary sequelae at high-resolution computed tomography (HRCT) through the assessment of laboratory data, lung function, and radiological changes in patients after the onset of COVID-19 interstitial pneumonia and the identification of predictive factors. METHODS: We enrolled 121 subjects hospitalized due to COVID-19 pneumonia in our study. Clinical features, Charlson Comorbidity Index (CCI) score, HRCT score, and blood chemistry data at hospital admission, as well as HRCT score, pulmonary function testing values, exercise capacity by means of a 6-Minute Walk Test (6MWT), and dyspnea perception by the modified Medical Research Council (mMRC) at 4-month follow-up, were all recorded. The variables were elaborated in order to create a predictive model to identify patients at high risk of pulmonary sequelae at HRCT. RESULTS: At the time of follow-up visit, 63% of patients had functional abnormality (diffusion lung capacity and/or total lung capacity <80% of predicted). Age, BMI, CCI, D-dimer, 6MWT, and mMRC were included in the COVID-19 Sequelae Score (COSeSco, ranging 0-15), which was able to individuate COVID-19 patients with radiologic sequelae (HRCT score >10%) at follow-up. The most revelatory COSeSco value that was found to intercept the highest sensitivity (100%) and specificity (77%) was 2. CONCLUSION: The COSeSco - comprising age, BMI, comorbidities, D-dimer, walking distance, and dyspnea perception - makes it possible to identify particularly at-risk COVID-19 patients who are likely to develop pulmonary sequelae assessed by HRCT.

Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy.

BACKGROUND: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy. OBJECTIVES: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy. METHOD: 238 subjects were submitted to molecular analysis of the SERPINA1 gene, and data on anthropometric variables, smoking habits, number of packs per year, AAT serum concentration, and clinical manifestations were recorded and presented as mean ± SD or median values (1st quartile; 3rd quartile). RESULTS: The results show a distribution of genetic AATD of 4.1% of the screened population in the area encompassing the city of Parma. PI*MS and PI*MZ were the most common genotypes at 40.9% and 28.2% of the population with genetic AATD, and asthma and emphysema were the most represented clinical manifestations. CONCLUSION: Our study allowed to increase the knowledge of the distribution of genetic AATD in Northern Italy providing information regarding frequencies of genotypes and clinical manifestations of the disorder.

Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. OBJECTIVES: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation. METHODS: We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system. RESULTS: The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (p = 0.014 and p = 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution. CONCLUSIONS: In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume.

BACKGROUND: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. OBJECTIVES: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. METHOD: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. RESULTS: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. CONCLUSIONS: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

Oral Corticosteroids Dependence and Biologic Drugs in Severe Asthma: Myths or Facts? A Systematic Review of Real-World Evidence.

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.

The interplay between diabetes mellitus and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) are common and chronic disorders. COPD is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities and it is considered currently the fourth leading cause of death worldwide. DM is a systemic disease characterized by a chronic hyperglycemia associated with inflammation and oxidative stress. The relationship between the two conditions is not completely understood and conflicting results are reported in the literature. Many studies have investigated the mechanisms through with the respiratory disease is associated with an increased risk of metabolic condition or whether the incidence risk of COPD in individuals affected by DM is higher. The link between the two chronic conditions has relevant implications in the management of patients affected by the both of them. Respiratory patients should be screened for diabetes mellitus as a frequent comorbidity of lung disease since therapeutic options should be assessed about risk-to-benefit ratios associated with the indication for the steroid use. Furthermore, the role of hyperglycemia on pulmonary function (e.g. infection or inflammatory processes) should be evaluated in DM. Finally, in presence of both diseases potential treatment interactions should be considered. In this overview we explored the common aspects of both clinical chronic illnesses and investigated the interplay between the two conditions.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Small airways in asthma: from bench-to-bedside.

INTRODUCTION: Historically, asthma was considered a disease predominantly of the large airways, but gradually small airways have been recognized as the major site of airflow obstruction. Small airway dysfunction (SAD) significantly contributes to the pathophysiology of asthma, and it is present across all asthma severities. Promising preclinical findings documented enhanced beneficial effects of combination therapies on small airways compared to monocomponents, thus it was questioned whether this could translate into further clinical implications from bench-to-bedside. The aim of this review was to systematically assess the state of the art of small airway involvement in asthma, especially in response to different pharmacological treatments acting on the respiratory system. EVIDENCE ACQUISITION: A comprehensive literature search was performed in MEDLINE for randomized controlled trials (RCTs) characterizing the impact on small airways of different pharmacological treatments acting on the respiratory system. The results were extracted and reported via qualitative synthesis. EVIDENCE SYNTHESIS: Overall, 63 studies were identified from the literature search, whereas 23 RCTs met the inclusion criteria. Evidence confirms that both drug particle size and the type of inhalation devices represent two of the most important variables for an effective peripheral lung distribution. CONCLUSIONS: Despite the numerous methodological tools to detect SAD, there is still no gold standard diagnostic method to assess small airways, especially in severe asthma. Further research should be directed to improve primary and secondary prevention strategies by supporting the combined approach of different non-invasive techniques for an early detection of peripheral abnormalities and optimization of asthma therapy.

Unexplained hypoxemia in COPD with cardiac shunt.

In Chronic Obstructive Pulmonary Disease (COPD), hypoxemia is associated with multiple underlying mechanisms, of which one of the most significant is ventilation-perfusion (V/Q) mismatch, which is correctable with supplemental oxygen (O2) therapy. Hypoxemia that is refractory to very high concentration of inspired O2 can be indicative of cardiac defect with shunt, e.g., a patent foramen ovale (PFO) with right-to-left (R-T-L) shunt. In hypoxemic COPD patients, the diagnosis of a PFO requires a heightened sense of clinical suspicion along with careful assessment of other underlying possibilities. Platypnea-orthodeoxia and a non-response to the hyperoxia test, while not diagnostic, increase suspicion. A correct diagnosis of interatrial bypass needs to be confirmed with transthoracic echocardiogram and contrast transesophageal echocardiography. Presently, no data are available supporting the effectiveness of PFO closure in COPD patients to relieve symptoms and correct hypoxemia. We report a case of hypoxemic COPD with platypnea-orthodeoxia syndrome due to PFO. The decision of its closure with device after echocardiographic evaluation of right ventricular function has completely corrected refractory hypoxemia with improvement of SpO2 and functional capacity. Thus, in selected COPD with refractory hypoxemia, closure of PFO should be considered as novel therapeutic target with improvement of quality of life and less likelihood of hospitalization.

Impact of Sex on Proper Use of Inhaler Devices in Asthma and COPD: A Systematic Review and Meta-Analysis.

Despite females being more often affected by asthma than males and the prevalence of COPD rising in females, conflicting evidence exists as to whether sex may modulate the correct inhaler technique. The aim of this study was to assess the impact of sex on the proper use of inhaler devices in asthma and COPD. A pairwise meta-analysis was performed on studies enrolling adult males and females with asthma or COPD and reporting data of patients making at least one error by inhaler device type (DPI, MDI, and SMI). The data of 6,571 patients with asthma or COPD were extracted from 12 studies. A moderate quality of evidence (GRADE +++) indicated that sex may influence the correct use of inhaler device in both asthma and COPD. The critical error rate was higher in females with asthma (OR 1.31, 95%CI 1.14−1.50) and COPD (OR 1.80, 95%CI 1.22−2.67) using DPI vs. males (p < 0.01). In addition, the use of SMI in COPD was associated with a greater rate of critical errors in females vs. males (OR 5.36, 95%CI 1.48−19.32; p < 0.05). No significant difference resulted for MDI. In conclusion, choosing the right inhaler device in agreement with sex may optimize the pharmacological treatment of asthma and COPD.

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma.

Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy. Although current pharmacological treatments improve symptom control, health status, and the frequency and severity of exacerbations, they do not really change the natural course of asthma, including disease remission. Considering the highly heterogeneous nature of asthma, there is a strong need for innovative medications that selectively target components of the inflammatory cascade. The aim of this review was to systematically assess current investigational agents in Phase I and II randomised controlled trials (RCTs) over the last five years. Sixteen classes of novel therapeutic options were identified from 19 RCTs. Drugs belonging to different classes, such as the anti-interleukin (IL)-4Rα inhibitors, anti-IL-5 monoclonal antibodies (mAbs), anti-IL-17A mAbs, anti-thymic stromal lymphopoietin (TSLP) mAbs, epithelial sodium channel (ENaC) inhibitors, bifunctional M3 receptor muscarinic antagonists/ß2-adrenoceptor agonists (MABAs), and anti-Fel d 1 mAbs, were found to be effective in the treatment of asthma, with lung function being the main assessed outcome across the RCTs. Several novel investigational molecules, particularly biologics, seem promising as future disease-modifying agents; nevertheless, further larger studies are required to confirm positive results from Phase I and II RCTs.

Stem Cell-Based Regenerative Therapy and Derived Products in COPD: A Systematic Review and Meta-Analysis.

COPD is an incurable disorder, characterized by a progressive alveolar tissue destruction and defective mechanisms of repair and defense leading to emphysema. Currently, treatment for COPD is exclusively symptomatic; therefore, stem cell-based therapies represent a promising therapeutic approach to regenerate damaged structures of the respiratory system and restore lung function. The aim of this study was to provide a quantitative synthesis of the efficacy profile of stem cell-based regenerative therapies and derived products in COPD patients. A systematic review and meta-analysis was performed according to PRISMA-P. Data from 371 COPD patients were extracted from 11 studies. Active treatments elicited a strong tendency towards significance in FEV1 improvement (+71 mL 95% CI -2−145; p = 0.056) and significantly increased 6MWT (52 m 95% CI 18−87; p < 0.05) vs. baseline or control. Active treatments did not reduce the risk of hospitalization due to acute exacerbations (RR 0.77 95% CI 0.40−1.49; p > 0.05). This study suggests that stem cell-based regenerative therapies and derived products may be effective to treat COPD patients, but the current evidence comes from small clinical trials. Large and well-designed randomized controlled trials are needed to really quantify the beneficial impact of stem cell-based regenerative therapy and derived products in COPD.

Platypnea-Orthodeoxia Syndrome after SARS-CoV-2 interstitial pneumonia: an overview and an update on our patient.

Platypnea-Orthodeoxia Syndrome (POS) is a clinical entity defined as positional dyspnoea (platypnea) and arterial desaturation (orthodeoxia) that occurs when sitting or standing up and usually resolves by lying down. Up to April 25th 2021, eleven cases of POS after SARS-CoV-2 pneumonia have been reported on Pubmed. Accordingly, SARS-CoV-2 infection may be considered as an emergent cause of POS due to an increase in ventilation/perfusion (V/Q) mismatch. In this article we provide an update on the patient with POS after fibrotic evolution of SARS-CoV-2 interstitial pneumonia, which we previously reported and we discuss the case reports of POS due to SARS-CoV-2 infection.

Beyond the lung involvement in COVID-19 patients.

Since COVID-19 spread all over the world becoming a pandemic illness, researchers have better characterized route of virus transmissibility and clinical signs and symptoms of the disease. Since viral transmission occurs through the droplets emitted during coughing or sneezing, the lungs are primarily affected. However, SARS-CoV-2 can affect several human organs due to high expressions of ACE2 receptor which is the main viral target, and the virus may affect not only higher and lower respiratory tracts, but also heart, kidney, gastro enteric tract, liver, pancreas, nervous system and skin. This review focuses on extra pulmonary involvement underlying atypical presentation of COVID-19. There is a great body of evidence concerning several human organ abnormalities associated to the SARS-CoV-2, enough to consider COVID-19 as a multisystemic and polyhedral disease.

Clinical manifestations of a new alpha-1 antitrypsin genetic variant: Q0parma.

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy.

An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

Sex-Related Differences in Long-COVID-19 Syndrome.

Background: Sex differences have been demonstrated in the acute phase of coronavirus disease 2019 (COVID-19). Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance. Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex. Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.