Home Noninvasive Ventilation in Myasthenia Gravis.

BACKGROUND: Noninvasive ventilation (NIV) plays an important role in avoiding endotracheal intubation during myasthenic crisis, yet there are few published data concerning long-term home NIV in stable out-patients with myasthenia gravis (MG). The aim of this study was to describe the prevalence of NIV in a cohort of subjects with stable MG and to analyze contributing factors that could predict the need of NIV. METHODS: We performed a cross-sectional study that included subjects diagnosed with MG managed in the respiratory care unit over the previous year. Subjects underwent clinical analysis including demographic, clinical, and functional respiratory data. RESULTS: Of the 50 subjects included, 35 (70%) were positive for nicotinic acetylcholine receptor antibodies, and 68% had a diagnosis of generalized MG. Bulbar symptoms developed in 16 (32%), and 10 (20%) subjects needed long-term home NIV. The only variable predicting the need for long-term NIV was MG severity measured with Myasthenia Gravis Foundation of America (MGFA), mainly grades IIB (odds ratio 0.14 [95% CI 0.02-0.85], P = .03) and IIIB (odds ratio 0.02 [95% CI 0.01-0.34], P = .01). CONCLUSIONS: Home NIV was needed in a substantial percentage of medically stable subjects with MG, mainly in those with generalized type and with oropharyngeal and/or respiratory muscle involvement (MGFA grades IIB and IIIB).

Frequency and characteristics of asthma in smokers attending smoking cessation units in Spain.

INTRODUCTION: The interaction between smoking and asthma impairs lung function and increases airflow obstruction severity. The identification of smoking patterns in smokers with and without asthma is crucial to provide the best care strategies. The aims of this study are to estimate asthma frequency, describe asthma features, and characterize smoking in smokers attending smoking cessation units. MATERIAL AND METHODS: We carried out a cross-sectional study in five smoking cessation units with different geographical distribution to estimate asthma frequency in smokers, characterize asthma features in smokers, as well as smoking in asthmatic smokers. RESULTS: Asthma frequency among smokers was 18.6%. Asthmatic smokers presented high passive exposure, low smoking self-efficacy and will to quit smoking, as well as a high exacerbation frequency, severe symptoms, and frequent use of long-acting beta agonists, inhaled steroids, and short-acting beta agonists. DISCUSSION: Smokers with asthma constitute a high-risk group with worsened evolution of pulmonary involvement. All smokers should be regularly screened for asthma. Effective smoking cessation strategies should be proposed to smokers with asthma in order to reverse the harmful effects of smoking on the airway, together with a comprehensive and integral approach.

Sample Treatment with Trypsin for RT-LAMP COVID-19 Diagnosis.

The SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic resulting in a global health emergency. Given its rapid spread and high number of infected individuals, a diagnostic tool for a rapid, simple, and cost-effective detection was essential. In this work, we developed a COVID-19 diagnostic test, that incorporates a human internal control, based on the Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP). When working with synthetic SARS-CoV-2 RNA, the optimized RT-LAMP assay has a sensitivity of 10 viral copies and can be detected by fluorescence in less than 15 min or by the naked eye in 25 min using colorimetric RT-LAMP. To avoid the RNA extraction step, a pre-treatment of the sample was optimized. Subsequently, a validation was performed on 268 trypsin treated samples (including nasopharyngeal, buccal, and nasal exudates) and amplified with colorimetric RT-LAMP to evaluate its sensitivity and specificity in comparison with RT-qPCR of extracted samples. The validation results showed a sensitivity and specificity of 100% for samples with Ct ≤ 30. The rapid, simple, and inexpensive RT-LAMP SARS-CoV-2 extraction-free procedure developed may be an alternative test that could be applied for the detection of SARS-CoV-2 or adapted to detect other viruses present in saliva or nasopharyngeal samples with higher sensitivity and specificity of the antibody test.

Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry.

Background: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited. Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs. Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005). Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM.

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and DlCO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006-1.00231; P = 0.003) and 12-month DlCO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000-1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

Post-COVID-19 Symptoms and Heart Disease: Incidence, Prognostic Factors, Outcomes and Vaccination: Results from a Multi-Center International Prospective Registry (HOPE 2).

BACKGROUND: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. METHODS: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. RESULTS: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81-3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04-0.19). CONCLUSIONS: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.

Consensus document on asthma and smoking of the Regional Asthma Forum of SEPAR. / Documento de consenso sobre asma y tabaquismo del Foro Autonómico de Asma de la SEPAR.

The prevalence of active smoking in adults with asthma is similar in the total population. Smoking is associated with worse clinical control of the disease, a rapid reduction of lung function and a variable response to corticoids. Tobacco consumption negatively affects the quality of life of asthmatic patients as well as increasing the number of medical visits and hospital admissions due to exacerbations. Moreover, smoking entails a higher risk of developing lung cancer, cardiovascular comorbidities and death in asthmatic patients. Nevertheless, current asthma guidelines do not include specific recommendations on the management of smoking asthmatic patients and the treatment of the smoking habit in this subpopulation. For this reason, a narrative review of the literature was carried out for consensus using a nominal group methodology developed throughout 2019 to extract practical recommendations that would allow the diagnosis and treatment of asthma in smokers, as well as the treatment of smoking in asthmatics, to be improved. The conclusions and recommendations were validated at the SEPAR national congress of the same year. Among the most relevant, the need to address smoking in people with asthma through health advice, pharmacological treatment and behavioral therapy was emphasized, as this is a factor that negatively impacts the symptoms, prognosis and response to asthma treatment. In smokers with suspected asthma, the presence of emphysema and the differential diagnosis of other diseases should be evaluated and the impact of smoking on the result of diagnostic tests should be considered. It is also concluded that smoking reduces the response to treatment with inhaled corticosteroids, which is why combined therapy with bronchodilators is recommended.

La prevalencia de tabaquismo activo en adultos con asma es similar a la de la población general. El tabaquismo se asocia con un peor control clínico de la enfermedad, una disminución acelerada de la función pulmonar y una respuesta irregular a la terapia con glucocorticoides. El consumo de tabaco impacta negativamente en la calidad de vida de los pacientes asmáticos y provoca un incremento en el número de visitas y de hospitalizaciones por exacerbaciones. Además, el tabaquismo aumenta el riesgo de cáncer de pulmón, comorbilidades cardiovasculares y muerte en pacientes asmáticos. A pesar de todo ello, las guías actuales del manejo del asma no incluyen recomendaciones específicas para el manejo de los pacientes asmáticos fumadores. Por este motivo, se procedió a una revisión narrativa de la literatura para un consenso mediante metodología de grupo nominal desarrollada a lo largo del año 2019 para extraer recomendaciones prácticas que permitieran mejorar el diagnóstico y el tratamiento del asma en fumadores, así como el tratamiento del tabaquismo en asmáticos. Las conclusiones y recomendaciones fueron validadas en el congreso nacional de la SEPAR del mismo año. Entre las más relevantes, se incidió en la necesidad de abordar el tabaquismo en las personas con asma mediante consejo sanitario, tratamiento farmacológico y terapia conductual, al ser un factor que impacta negativamente en la sintomatología, el pronóstico y la respuesta al tratamiento del asma. En el fumador con sospecha de asma, se debe evaluar la presencia de enfisema y el diagnóstico diferencial de otras enfermedades y considerar el impacto del tabaquismo en el resultado de las pruebas diagnósticas. También se concluye que el hábito tabáquico reduce la respuesta al tratamiento con corticoides inhalados, por lo que se recomienda terapia combinada con broncodilatadores.

Documento de consenso sobre asma y tabaquismo del Foro Autonómico de Asma de la SEPAR / Consensus document on asthma and smoking of the Regional Asthma Forum of SEPAR

La prevalencia de tabaquismo activo en adultos con asma es similar ala de la población general. El tabaquismo se asocia con un peor control clínico de la enfermedad, una disminución acelerada de la función pulmonar y una respuesta irregular a la terapia con glucocorticoides. El consumo de tabaco impacta negativamente en la calidad devida de los pacientes asmáticos y provoca un incremento en el númerode visitas y de hospitalizaciones por exacerbaciones. Además, el tabaquismo aumenta el riesgo de cáncer de pulmón, comorbilidades cardiovasculares y muerte en pacientes asmáticos. A pesar de todo ello,las guías actuales del manejo del asma no incluyen recomendacionesespecíficas para el manejo de los pacientes asmáticos fumadores. Poreste motivo, se procedió a una revisión narrativa de la literatura paraun consenso mediante metodología de grupo nominal desarrolladaa lo largo del año 2019 para extraer recomendaciones prácticas quepermitieran mejorar el diagnóstico y el tratamiento del asma en fumadores, así como el tratamiento del tabaquismo en asmáticos. Lasconclusiones y recomendaciones fueron validadas en el congreso nacional de la SEPAR del mismo año. Entre las más relevantes, se incidió en la necesidad de abordar el tabaquismo en las personas conasma mediante consejo sanitario, tratamiento farmacológico y terapiaconductual, al ser un factor que impacta negativamente en la sintomatología, el pronóstico y la respuesta al tratamiento del asma. En elfumador con sospecha de asma, se debe evaluar la presencia de enfisema y el diagnóstico diferencial de otras enfermedades y considerarel impacto del tabaquismo en el resultado de las pruebas diagnósticas.También se concluye que el hábito tabáquico reduce la respuesta altratamiento con corticoides inhalados, por lo que se recomienda terapia combinada con broncodilatadores. (AU)

The prevalence of active smoking in adults with asthma is similar inthe total population. Smoking is associated with worse clinical control of the disease, a rapid reduction of lung function and a variableresponse to corticoids. Tobacco consumption negatively affects thequality of life of asthmatic patients as well as increasing the numberof medical visits and hospital admissions due to exacerbations. Moreover, smoking entails a higher risk of developing lung cancer, cardiovascular comorbidities and death in asthmatic patients. Nevertheless,current asthma guidelines do not include specific recommendationson the management of smoking asthmatic patients and the treatmentof the smoking habit in this subpopulation. For this reason, a narrativereview of the literature was carried out for consensus using a nominalgroup methodology developed throughout 2019 to extract practicalrecommendations that would allow the diagnosis and treatment ofasthma in smokers, as well as the treatment of smoking in asthmatics,to be improved. The conclusions and recommendations were validated at the SEPAR national congress of the same year. Among the mostrelevant, the need to address smoking in people with asthma throughhealth advice, pharmacological treatment and behavioral therapy wasemphasized, as this is a factor that negatively impacts the symptoms,prognosis and response to asthma treatment. In smokers with suspected asthma, the presence of emphysema and the differential diagnosisof other diseases should be evaluated and the impact of smoking onthe result of diagnostic tests should be considered. It is also concluded that smoking reduces the response to treatment with inhaled corticosteroids, which is why combined therapy with bronchodilators isrecommended (AU)

Idiopathic Pulmonary Fibrosis and Telomeres.

Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology with a highly compromised prognosis and a significant mortality rate within a few years of diagnosis. Despite being idiopathic, it has been shown that telomeric shortening could play an important role in its etiopathogenesis. Mutations in telomere-related genes have been identified, but they are not always present despite telomere shortening. On the other hand, this telomeric shortening has been linked to a worse prognosis of the disease independently of other clinical factors, implying it may serve as a biomarker.

Lung function and radiological findings 1 year after COVID-19: a prospective follow-up.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. METHODS: COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. RESULTS: Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06-2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98-0.99; p = 0.046). CONCLUSION: Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020).

The radiographic assessment of lung edema score of lung edema severity correlates with inflammatory parameters in patients with coronavirus disease 2019-Potential new admission biomarkers to predict coronavirus disease 2019 worsening.

Background: Coronavirus disease 2019 (COVID-19) has placed enormous pressure on intensive care units (ICUs) and on healthcare systems in general. A deeper understanding of the pathophysiology of the most severe forms of COVID-19 would help guide the development of more effective interventions. Herein, we characterized the inflammatory state of patients with COVID-19 of varying degrees of severity to identify admission biomarkers for predicting COVID-19 worsening. Design: Admission blood samples were obtained from 78 patients with COVID-19. Radiographic assessment of lung edema (RALE) scoring was calculated by imaging. Platelet and leukocyte counts were measured by flow cytometry, and plasma levels of C-reactive protein were assessed by immunoturbidimetry, and interleukin (IL)-8/CXCL8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monocyte chemoattractant protein-1 (MCP-1/CCL2) levels by enzyme-linked immunosorbent assay (ELISA). Results: The RALE score correlated with several admission hemogram (platelets, neutrophils, and lymphocytes) and inflammatory (IL-8/CXCL8, MCP-1/CCL2, IL-10, and C-reactive protein) parameters. COVID-19 worsening, based on the need for oxygen (Δoxygen supply) during hospitalization, correlated negatively with admission lymphocyte counts but positively with neutrophil-to-lymphocyte ratio and with plasma levels of the inflammatory parameters correlating with RALE score. Conclusion: Our data indicate a correlation between the RALE score and Δoxygen supply and admission inflammatory status. The identification of a panel of biomarkers that reflect COVID severity might be useful to predict disease worsening during hospitalization and to guide clinical management of COVID-19-related complications. Finally, therapies targeting IL-8/CXCL8- or IL-10 activity may offer therapeutic approaches in COVID-19 treatment.

Waveforms Analysis in Patients With Amyotrophic Lateral Sclerosis for Enhanced Efficacy of Mechanically Assisted Coughing.

BACKGROUND: Effectiveness of mechanical assisted coughing with insufflation-exsufflation (MI-E) in amyotrophic lateral sclerosis (ALS) depends largely on severity of bulbar dysfunction, which can generate different upper-airway responses. The aim of the study was to evaluate the use of graphs generated by MI-E in ALS to detect airway obstruction and set parameters to achieve an effective mechanically assisted coughing. METHODS: This was a prospective study enrolling patients with ALS. Several sessions with MI-E were applied, administering different insufflation-exsufflation (± 20, ± 30, ± 40, ± 50 cm H2O) levels in each session. The graphs produced were recorded and analyzed, and the results were used to select the parameters resulting in more effective MI-E. RESULTS: Sixty-nine subjects with ALS were included, yielding a total of 351 analyzed records. A pattern of obstruction during insufflation was detected in 34 subjects (50.7%) and of upper-airway collapse during exsufflation in 18 subjects (26%). The variable associated with obstruction during insufflation was bulbar upper motor neuron dysfunction (odds ratio 7.19 [95% CI 2.32-22.29], P = .001), whereas bulbar lower motor neuron dysfunction was related to upper-airway collapse during exsufflation (odds ratio 0.32 [95% CI 0.11-0.98], P = .046). After parameters were adjusted, in 68 subjects (98.55%) an effective MI-E was achieved. The only variable that predicted absence of alterations in the graphs was Norris bulbar score (odds ratio 0.87 [95% CI 0.78-0.96], P = .007). CONCLUSIONS: Analysis of graphics generated by applying MI-E in ALS was an effective method to detect upper-airway responses and select optimal set parameters. Obstruction during insufflation is related to bulbar upper motor neuron dysfunction and collapse during exsufflation to bulbar lower motor neuron dysfunction.

Lung Fibrosis and Fibrosis in the Lungs: Is It All about Myofibroblasts?

In the lungs, fibrosis is a growing clinical problem that results in shortness of breath and can end up in respiratory failure. Even though the main fibrotic disease affecting the lung is idiopathic pulmonary fibrosis (IPF), which affects the interstitial space, there are many fibrotic events that have high and dangerous consequences for the lungs. Asthma, chronic obstructive pulmonary disease (COPD), excessive allergies, clearance of infection or COVID-19, all are frequent diseases that show lung fibrosis. In this review, we describe the different kinds of fibrosis and analyse the main types of cells involved-myofibroblasts and other cells, like macrophages-and review the main fibrotic mechanisms. Finally, we analyse present treatments for fibrosis in the lungs and highlight potential targets for anti-fibrotic therapies.