Histological and Ultrastructural Changes in Lungs One Year Post Asymptomatic or Mild SARS-CoV-2 Infection: Evaluating the Potential for Active Virus Presence / Cambios Histológicos y Ultraestructurales en los Pulmones un Año Después de una Infección Asintomática o Leve por SARS-CoV-2: Evaluación del Potencial de Presencia Activa del Virus

SUMMARY: Prior research on post-COVID-19 or long COVID primarily focused on the presence of SARS-CoV-2 mostly in symptomatic patients. This study aimed to investigate the persistence of SARS-CoV-2 after 1 year of asymptomatic or mild COVID-19. SARS-CoV-2 infected and control K18-hACE2 transgenic mice (n=25) were studied. Moderate and severe symptomatic subjects were sacrificed after eight days, while mild or asymptomatic mice were kept in BSL-III for twelve months. Analyses included general condition, histochemistry, immunohistochemistry, transmission electron microscopy, and qRT-PCR. Lungs from the twelve-month group showed thickening of alveolar walls, with some lungs exhibiting the recruitment of inflammatory cells, the presence of SARS- CoV-2 mRNA, immunopositivity for the SARS-CoV-2 spike protein, and TEM showed viruses (60-125 nm) within vesicles, indicating continued replication. Certain lung samples showed persistent SARS-CoV-2 presence in Club cells, endothelial cells, and macrophages. The eight-day group exhibited viral interstitial pneumonitis, SARS-CoV-2 immunopositivity, and mRNA. The eight-day hearts displayed viral mRNA, while the twelve-month hearts tested negative. Some asymptomatic twelve-month subjects presented reduced surfactant, basal membrane thickening, fibrosis, and mild autonomic nerve degeneration. In this study conducted on mice, findings indicate the potential for chronic persistence of SARS-CoV-2 in the lungs one year post initial mild or asymptomatic infection, which could suggest the possibility of recurrent episodes in similar human conditions. The observed thickening of alveolar walls and potential fibrotic areas in these mice may imply an increased risk of post-COVID fibrosis in humans. Furthermore, the presence of SARS-CoV-2-positive inflammatory cells in some asymptomatic murine cases could herald a progression toward ongoing inflammation and chronic lung disease in humans. Therefore, the necessity for further studies in human subjects and vigilant monitoring of high-risk human populations is underscored.

Investigaciones anteriores sobre COVID-19 o COVID prolongado se centraron principalmente en la presencia de SARS-CoV-2 principalmente en pacientes sintomáticos. Este estudio tuvo como objetivo investigar la persistencia del SARS-CoV-2 después de 1 año de COVID-19 asintomático o leve. Se estudiaron ratones transgénicos K18-hACE2 infectados con SARS-CoV-2 y de control (n=25). Los animales con síntomas moderados y graves se sacrificaron después de ocho días, mientras que los ratones con síntomas leves o asintomáticos se mantuvieron en BSL-III durante doce meses. Los análisis incluyeron estado general, histoquímica, inmunohistoquímica, microscopía electrónica de transmisión y qRT- PCR. Los pulmones del grupo de doce meses mostraron engrosamiento de las paredes alveolares, y algunos pulmones exhibieron reclutamiento de células inflamatorias, presencia de ARNm del SARS-CoV-2, inmunopositividad para la proteína de la espícula del SARS-CoV-2 y TEM mostró virus (60 -125 nm) dentro de las vesículas, lo que indica una replicación continua. Ciertas muestras de pulmón mostraron una presencia persistente de SARS- CoV-2 en exocrinocitos bronquiolares, células endoteliales y macrófagos. El grupo de ocho días presentó neumonitis intersticial viral, inmunopositividad al SARS-CoV-2 y ARNm. Los corazones de ocho días mostraron ARNm viral, mientras que los corazones de doce meses dieron negativo. Algunos animales asintomáticos de doce meses presentaron disminución del surfactante, engrosamiento de la membrana basal, fibrosis y degeneración leve del nervio autónomo. En este estudio realizado en ratones, los hallazgos indican la posibilidad de persistencia crónica del SARS-CoV-2 en los pulmones un año después de la infección inicial leve o asintomática, lo que podría sugerir la posibilidad de episodios recurrentes en condiciones humanas similares. El engrosamiento observado de las paredes alveolares y las posibles áreas fibróticas en estos ratones puede implicar un mayor riesgo de fibrosis post-COVID en humanos. Además, la presencia de células inflamatorias positivas para SARS- CoV-2 en algunos casos murinos asintomáticos podría presagiar una progresión hacia una inflamación continua y una enfermedad pulmonar crónica en humanos. Por lo tanto, se subraya la necesidad de realizar más estudios en seres humanos y realizar un seguimiento atento de las poblaciones humanas de alto riesgo.

Presentación de 11 pacientes con el diagnóstico de agenesia e hipoplasia pulmonar diagnosticados en un periodo de 24 años y revisión de la literatura / Presentation of 11 patients diagnosed with pulmonary agenesis and hypoplasia over a period of 24 years and a review of the literature

La agenesia pulmonar (AgP), la aplasia pulmonar (AP) e hipoplasia pulmonar (HP) son malformaciones congénitas poco comunes. En la AgP, no se desarrollan el bronquio ni el pulmón; en la AP, hay un bronquio rudimentario sin parénquima pulmonar; y en la HP, uno o ambos pulmones presentan un tamaño reducido debido a trastornos en su crecimiento. Las causas de la AgP, AP y HP pueden ser tanto primarias como secundarias, predominando estas últimas. Entre ellas se incluyen: oligohidroamnios, anomalías esqueléticas, enfermedades neuromusculares, hernia diafragmática, malformaciones vasculares, cardiopatías complejas, genopatías y cromosomopatías. El rango de manifestaciones varía desde pacientes asintomáticos hasta aquellos con dificultad respiratoria neonatal de leve a severa. Con el tiempo, algunos pacientes pueden experimentar neumonías recurrentes y progresar hacia una enfermedad pulmonar crónica (EPC). La imagenología juega un papel crucial en el diagnóstico. El pronóstico está fuertemente influenciado por la presencia de otras malformaciones congénitas. Generalmente, el enfoque terapéutico es conservador. Este artículo detalla la presentación clínica y la evolución a lo largo de 24 años de 11 pacientes diagnosticados con AgP o HP.

Pulmonary agenesis (AgP), aplasia (AP), and hypoplasia (HP) are rare congenital malformations. In AgP, there is no development of the bronchus or lung; in AP, a rudimentary bronchus is present without lung parenchyma; and in HP, one or both lungs are reduced in size due to growth disorders. The causes of AgP, AP, and HP can be either primary or secondary, with the latter being more common. Examples include oligohydramnios, skeletal anomalies, neuromuscular diseases, diaphragmatic hernia, vascular malformations, complex heart diseases, genopathies, and chromosomal disorders. The spectrum of manifestations ranges from asymptomatic patients to those with mild to severe neonatal respiratory distress. Over time, some patients may experience recurrent pneumonias and progress to chronic lung disease (CLD). Imaging studies are crucial for diagnosis. The prognosis primarily depends on the presence of other congenital malformations. The treatment approach is generally conservative. This article describes the clinical presentation and evolution over 24 years of 11 patients diagnosed with AgP or HP.

Mortalidade por câncer de traqueia, brônquios e pulmões no Nordeste do Brasil, 2002-2019 / Mortalidad por cáncer de tráquea, bronquios y pulmones en el Nordeste de Brasil, 2002- 2019 / Mortality from cancer of the trachea, bronchi and lungs in Northeast Brazil, 2002-2019

Objetivo: analisar a distribuição e taxa de mortalidade por câncer de traqueia, brônquios e pulmão nos Estados da Região Nordeste do Brasil, entre os anos de 2002 e 2019. Método: estudo ecológico, cujos dados foram coletados do Instituto Brasileiro de Geografia e Estatística e do Atlas On-line de Mortalidade por Câncer. Resultados: foram registrados 70.578 óbitos por câncer de traqueia, brônquios e pulmões na Região Nordeste do Brasil, ao longo dos anos, com uma média anual de aproximadamente 4.151 óbitos. Dentre esse total a maioria foram do sexo masculino, mas quando comparado à variação percentual anual estimada entre os sexos, observou-se que em todos os Estados a variação do sexo feminino foi maior. Conclusão: os Estados do Ceará, Bahia e Pernambuco possui os números mais elevados de óbitos do Nordeste. E os Estados Paraíba, Maranhão e Piauí que apresentaram 7,01, 6,15 e 4,65 de variação.(AU)

Objective: to analyze the distribution and mortality rate from trachea, bronchi and lung cancer in the states of the Northeast Region of Brazil, between 2002 and 2019. Method: ecological study, whose data were collected from the Brazilian Institute of Geography and Statistics and from the Online Atlas of Cancer Mortality. Results: 70,578 deaths from cancer of the trachea, bronchi and lungs were recorded in the Northeast region of Brazil, over the years, with an annual average of approximately 4,151 deaths. Among this total, the majority were male, but when compared to the estimated annual percentage variation between the sexes, it was observed that in all states the variation of females was greater. Conclusion: the states of Ceará, Bahia and Pernambuco have the highest numbers of deaths in the Northeast. And the states of Paraíba, Maranhão and Piauí that presented 7.01, 6.15 and 4.65 of estimated annual percent change.(AU)

Objetivo: analizar la distribución y tasa de mortalidad por cáncer de tráquea, bronquios y pulmón en los Estados de la Región Nordeste de Brasil, entre 2002 y 2019. Método: estudio ecológico, cuyos datos fueron recolectados del Instituto Brasileño de Geografía y Estadística y de Atlas en línea de mortalidad por cáncer. Resultados: se registraron 70.578 muertes por cáncer de tráquea, bronquios y pulmones en la región Nordeste de Brasil, a lo largo de los años, con un promedio anual de aproximadamente 4.151 muertes. Dentro de este total, la mayoría eran hombres, pero al comparar la variación porcentual anual estimada entre los sexos, se observó que en todos los Estados la variación del sexo femenino fue mayor. Conclusión: los Estados de Ceará, Bahía y Pernambuco tienen los mayores números de muertes en el Nordeste. Y los Estados de Paraíba, Maranhão y Piauí que presentaron 7,01, 6,15 y 4,65 de variación porcentual anual estimado, respectivamente.(AU)

Evaluation of D-dimer as a predictor of severity, degree of pulmonary involvement and mortality in patients with COVID-19 / Avaliação do D-dímero como preditor de gravidade, grau de envolvimento pulmonar e mortalidade em pacientes com COVID-19

Objective: To verify D-dimer values to predict disease severity, degree of lung involvement and mortality in patients with COVID-19. Method: The D-dimer levels of 200 confirmed COVID-19 patients were prospectively measured in the Emergency Department of Razi Hospital of Ahvaz on the admission day, and its relations with the illness severity, computed tomography (CT) score, and mortality were assessed. Results: D-dimer level > 1.04 µg/mL and ≤ 1.12 µg/mL could indicate severe illness and high grade of pulmonary involvement but low risk of death. The mortality rate in the patients with D-dimer level > 1.12 µg/mL (was significantly higher than its rate in those with D-dimer level ≤ 1.12 µg/mL (17.2% x 1.5%; P:0.02). An independent positive correlation was found between D-dimer and Chest CT score as well as the disease severity (OR: 1.84; 95%CI:1.38 - 2.45; P:0.0001). Conclusion: D-dimer level > 1.12 µg/mL on the early stage of COVID-19 infection may independently predict the severe illness, high grade of pulmonary involvement, and high risk of death, indicating its beneficial role in timely management of critical patients.

Objetivo: Verificar os valores do D-dímero para predizer a gravidade da doença, o grau de envolvimento pulmonar e a mortalidade em pacientes com COVID-19. Método: Os níveis de dímero D de 200 pacientes confirmados com COVID-19 foram medidos, prospectivamente, no Departamento de Emergência do Hospital Razi de Ahvaz, no dia da admissão, e suas relações com a gravidade da doença, escore de tomografia computadorizada (CT) e mortalidade foram avaliadas. Resultados: Os níveis do D-dímero > 1,04 µg/mL e ≤ 1,12 µg/mL podem indicar doença grave e alto grau de envolvimento pulmonar, mas baixo risco de morte. A taxa de mortalidade nos pacientes com valor de D-dímero > 1,12 µg/mL foi significativamente maior do naqueles com nível de D-dímero ≤ 1,12 µg/mL (17,2% x 1,5%; P:0,02). Foi encontrada uma correlação positiva independente entre o D-dímero e o escore de CT de tórax e a gravidade da doença (OR: 1,84; IC 95%:1,38 - 2,45; P:0,0001). Conclusão: O nível do D-dímero > 1,12 µg/mL no estágio inicial da infecção por COVID-19 pode prever independentemente a doença grave, alto grau de envolvimento pulmonar e alto risco de morte, indicando seu papel benéfico no manejo oportuno de pacientes críticos.

Efficacy and safety of combined doxofylline and salbutamol in treatment of acute exacerbation of chronic obstructive pulmonary disease

SUMMARY OBJECTIVE: The aim of this study was to investigate the efficacy and safety of combined doxofylline and salbutamol in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 68 acute exacerbation of chronic obstructive pulmonary disease patients were randomly divided into control group (34 cases) and experimental group (34 cases), who received the doxofylline treatment and combined doxofylline and salbutamol treatment for 1 week, respectively. During the treatment, the remission time of typical respiratory manifestations was recorded, and the adverse reactions were observed. At the end of treatment, the treatment efficacy was evaluated. Before and after treatment, the pulmonary function indexes and serological indicators were detected. RESULTS: After treatment, compared with control group, in experimental group, the effective rate of treatment was significantly increased (p<0.05), the remission time of typical respiratory manifestations was significantly shortened (p<0.05), the pulmonary function indexes were significantly improved (p<0.05), the serum high-sensitivity C-reactive protein and cystatin C levels were significantly decreased, respectively (p<0.05), and the serum prealbumin level was significantly increased (p<0.05). In addition, the adverse reaction rate had no significant difference between two groups (p>0.05). CONCLUSIONS: In the treatment of acute exacerbation of chronic obstructive pulmonary disease, the combined use of doxofylline and salbutamol can quickly relieve the respiratory symptoms, mitigate the pulmonary dysfunction, and reduce the inflammatory response, thus promoting the outcome of patients.

Lesão pulmonar autoinflingida: é possível identificar o risco? Relato de caso / Self-inflicted lung injury: is it possible to identify the risk? A case report

RESUMO A respiração espontânea pode ser prejudicial para pacientes com pulmões previamente lesados, especialmente na vigência de síndrome do desconforto respiratório agudo. Mais ainda, a incapacidade de assumir a respiração totalmente espontânea durante a ventilação mecânica e a necessidade de voltar à ventilação mecânica controlada se associam com mortalidade mais alta. Existe uma lacuna no conhecimento em relação aos parâmetros que poderiam ser úteis para predizer o risco de lesão pulmonar autoinflingida pelo paciente e detecção da incapacidade de assumir a respiração espontânea. Relata-se o caso de um paciente com lesão pulmonar autoinflingida e as correspondentes variáveis, básicas e avançadas, de monitoramento da mecânica do sistema respiratório, além dos resultados fisiológicos e clínicos relacionados à respiração espontânea durante ventilação mecânica. O paciente era um homem caucasiano com 33 anos de idade e história clínica de AIDS, que apresentou síndrome do desconforto respiratório agudo e necessitou ser submetido à ventilação mecânica invasiva após falha do suporte ventilatório não invasivo. Durante os períodos de ventilação controlada, adotou-se estratégia de ventilação protetora, e o paciente mostrou evidente melhora, tanto do ponto de vista clínico quanto radiográfico. Contudo, durante cada período de respiração espontânea sob ventilação com pressão de suporte, apesar dos parâmetros iniciais adequados, das regulagens rigorosamente estabelecidas e do estrito monitoramento, o paciente desenvolveu hipoxemia progressiva e piora da mecânica do sistema respiratório, com deterioração radiográfica claramente correlacionada (lesão pulmonar autoinflingida pelo paciente). Após falha de três tentativas de respiração espontânea, o paciente faleceu por hipoxemia refratária no 29° dia. Neste caso, as variáveis básicas e avançadas convencionais não foram suficientes para identificar a aptidão para respirar espontaneamente ou predizer o risco de desenvolver lesão pulmonar autoinflingida pelo paciente durante a ventilação de suporte parcial.

ABSTRACT Spontaneous breathing can be deleterious in patients with previously injured lungs, especially in acute respiratory distress syndrome. Moreover, the failure to assume spontaneous breathing during mechanical ventilation and the need to switch back to controlled mechanical ventilation are associated with higher mortality. There is a gap of knowledge regarding which parameters might be useful to predict the risk of patient self-inflicted lung injury and to detect the inability to assume spontaneous breathing. We report a case of patient self-inflicted lung injury, the corresponding basic and advanced monitoring of the respiratory system mechanics and physiological and clinical results related to spontaneous breathing. The patient was a 33-year-old Caucasian man with a medical history of AIDS who developed acute respiratory distress syndrome and needed invasive mechanical ventilation after noninvasive ventilatory support failure. During the controlled ventilation periods, a protective ventilation strategy was adopted, and the patient showed clear clinical and radiographic improvement. However, during each spontaneous breathing period under pressure support ventilation, despite adequate initial parameters and a strictly adjusted ventilatory setting and monitoring, the patient developed progressive hypoxemia and worsening of respiratory system mechanics with a clearly correlated radiographic deterioration (patient self-inflicted lung injury). After failing three spontaneous breathing assumption trials, he died on day 29 due to refractory hypoxemia. Conventional basic and advanced monitoring variables in this case were not sufficient to identify the aptitude to breathe spontaneously or to predict the risk and development of patient self-inflicted lung injury during partial support ventilation.

Uso de ultrasonido pulmonar para predecir mortalidad intrahospitalaria en pacientes con infección por COVID-19 / Use of pulmonary ultrasound to predict in-hospital mortality in patients with COVID-19 infection

Resumen Introducción: La implementación del ultrasonido pulmonar (LUS) en los pacientes con COVID-19 puede ayudar a establecer el grado de afectación pulmonar, evaluar la respuesta al tratamiento y estimar el desenlace intrahospitalario. Objetivo: Evaluar la aplicación de un protocolo LUS en pacientes con infección por COVID-19 para predecir mortalidad intrahospitalaria. Métodos: El estudio se realizó del 1 de abril al 1 de agosto de 2020 en pacientes con infección por COVID-19, ingresados en la Unidad de Terapia Intensiva. Se realizó evaluación pulmonar por médicos entrenados en ultrasonografía crítica. Resultados: La mayoría de los pacientes fue del sexo masculino, la edad mediana fue de 56 años y 59 % requirió ventilación mecánica. La mortalidad intrahospitalaria fue de 39.4 % y en aquellos con puntuación de LUS ≥ 19, de 50 %. El modelo de regresión logística múltiple mostró que la puntuación de LUS ≥ 19 se asoció significativamente a mortalidad (cociente de riesgo = 2.55, p = 0.01). Conclusiones: El LUS es una herramienta clínica segura y rápida que puede realizarse al lado de la cama de los pacientes con infección por COVID-19, para establecer el grado de afectación parenquimatosa y predecir la mortalidad.

Abstract Introduction: Lung ultrasound (LUS) implementation in patients with COVID-19 can help to establish the degree of pulmonary involvement, evaluate treatment response and estimate in-hospital outcome. Objective: To evaluate the application of LUS in patients with COVID-19 infection to predict in-hospital mortality. Methods: The study was carried out from April 1 to August 1, 2020 in patients with COVID-19 infection admitted to the Intensive Care Unit. Lung evaluation was carried out by physicians trained in critical care ultrasonography. Results: Most patients were males, median age was 56 years, and 59 % required mechanical ventilation. In-hospital mortality was 39.4 %, and in those with a LUS score ≥ 19, mortality was higher (50 %). The multiple logistic regression model showed that a LUS score ≥ 19 was significantly associated with mortality (hazard ratio = 2.55, p = 0.01). Conclusions: LUS is a safe and fast clinical tool that can be applied at bedside in patients with COVID-19 infection to establish the degree of parenchymal involvement and predict mortality.

Bacterial pneumonia in captive wild boars in southern Brazil: etiological and pathological causes

Respiratory diseases are one of the major health issues described in intensive pig production, causing important economic losses. However, there is little information on the prevalence, etiology and clinical-pathological presentation of these diseases in wild boars. For this reason, this work investigated the presence in captive wild boars of pneumonic lesions and bacterial pathogens commonly detected and associated with respiratory diseases in domestic pigs. A total of 226 captive wild boar lungs from two farms were examined in a slaughterhouse in Southern Brazil. The pneumonic lesions were classified as cranioventral, dorsocaudal, and disseminated, and the quantification of lesions was calculated. From the total of 226 lungs, 121 were collected for laboratory examination. Lungs with macroscopic lesions suggestive of pneumonia were collected for histological, bacteriological and molecular analysis. The molecular analysis was performed to detect the presence of Actinobacillus (A.) pleuropneumoniae, Glaesserella (G.) parasuis, Mycoplasma (M.) hyopneumoniae, Mycoplasma (M.) hyorhinis and Streptococcus (S.) suis serotype 2. The percentages of histological lesions and bacterial agents and their association were calculated. Cranioventral consolidation (75.2%) was the most prevalent macroscopic lung lesion, followed by disseminated (21.5%) and dorsocaudal (3.3%) distribution. Microscopically, chronic lesions were the most prevalent, representing 70.2% of the lungs. Moreover, BALT hyperplasia was present in 86.5% of the lungs, suppurative bronchopneumonia in 65.7%, and alveoli infiltrate in 46.8%. Six bacterial pathogens commonly described as agents of pig pneumonia were identified by bacterial or molecular methods: Pasteurella (P.) multocida, S. suis, M. hyopneumoniae, A. pleuropneumoniae, G. parasuis and M. hyorhinis. Twenty-eight different combinations of pathogens were identified in 84 samples (69.4%). The most common combinations were: M. hyopneumoniae and A. pleuropneumoniae (13.1%), M. hyopneumoniae, G. parasuis and M. hyorhinis (10.7%), and M. hyopneumoniae, A. pleuropneumoniae and G. parasuis (8.3%). Additionally, M. hyopneumoniae was the most frequent pathogen detected in this study, representing 58.7% of the samples. The detection of M. hyopneumoniae and M. hyorhinis by PCR was associated with the presence of BALT hyperplasia (P < 0.05) and there was also an association between the detection of M. hyopneumoniae by PCR and suppurative bronchopneumonia (P < 0.05). In addition, a significant association (P < 0.05) between the detection of M. hyopneumoniae and A. pleuropneumoniae by PCR and the histological classification (acute, subacute or chronic lesions) was observed. The results of this study were similar to those observed in slaughtered domestic pigs, although, the detection of opportunist pathogens was less frequent than that usually described in pig pneumonia. The high prevalence of pneumonia in captive wild boars at slaughter and the similar characteristics of pneumonia in captive wild boars and domestic pigs suggest that the close phylogenetic relationship between pigs and wild boars could influence the susceptibility of both species to the colonization of the same pathogens, indicating that captive wild boars raised in confined conditions could be predisposed to respiratory diseases, similar to domestic pigs.(AU)

Relação do tempo de trânsito faríngeo e presença de resíduo com dispneia e função pulmonar na doença pulmonar obstrutiva crônica / Relationship of pharyngeal transition time and presence of residue with dyspnea and lung function in chronic obstructive pulmonary disease

RESUMO Objetivo Relacionar o tempo de trânsito faríngeo e a presença de resíduos com a dispneia e a função pulmonar em indivíduos com Doença Pulmonar Obstrutiva Crônica DPOC. Método Estudo realizado com 19 adultos (11 homens e 8 mulheres) com diagnóstico clínico e espirométrico de DPOC e idade média de 63,8 (±9,3) anos. A coleta de dados foi realizada utilizando o questionário COPD Assessment Test (CAT, Teste de Avaliação da DPOC) a escala de dispneia do Medical Research Council modificada (mMRC) e um manovacuômetro digital, para caracterizar o impacto da doença no indivíduo, a dispneia e a função pulmonar. Os dados referentes ao tempo de trânsito faríngeo e resíduo faríngeo foram coletados por meio de análise das imagens videofluoroscópicas realizada por três juízes cegados. Resultados Não foram encontradas relações significativas entre tempo de trânsito faríngeo (TTF) com função pulmonar (r = -0,71), e entre presença de resíduo faríngeo com a dispneia (r= -0,06). O TTF, quando comparado com a normalidade, apresentou-se aumentado. Conclusão Os indivíduos com DPOC, independente da gravidade da doença, não manifestaram associação entre alterações no TTF e resíduo faríngeo e dispneia e função pulmonar.

ABSTRACT Purpose To relate pharyngeal transit time and the presence of residues with dyspnea and lung function in individuals with Chronic Obstructive Pulmonary Disease COPD. Methods Study conducted with 19 adults (11 men, 8 women) with a clinical and spirometric diagnosis of COPD and a mean age of 63.8 years (SD = 9.3). Data collection was performed using the COPD Assessment Test (CAT) questionnaire, the modified Medical Research Council scale (mMRC) and a digital manovacuometer, to characterize the impact of the disease on the individual, dyspnea and lung function. The data related to pharyngeal transit time and pharyngeal residue were collected through the analysis of videofluoroscopic images performed by three blinded judges. Results No significant relationship was found between pharyngeal transit time (PTT) with lung function (r = -0.71), pharyngeal residue and dyspnea (r = -0.06). PTT, when compared to normality, was increased. Conclusion Individuals with COPD, regardless of the severity of the disease, showed no association between PTT and pharyngeal residue and dyspnea and lung function.

Insulina modula migração celular e a secreção de citocinas na vigência da infecção pulmonar por Paracoccidioides brasiliensis em camundongos diabéticos e não-diabéticos / Insulin modulates cell migration and cytokines secretion during pulmonary infection caused by Paracoccidioides brasiliensis in diabetic and non-diabetic mice

Diabetes mellitus (DM) compreende um conjunto de doenças metabólicas de grande importância e incidência mundial. Nele, o DM do tipo 1 é caracterizado pela destruição de células pancreáticas produtoras de insulina, e dentre seus sintomas, a disfunção imunológica relacionada à falta de insulina foi observada por diversos estudos, descrevendo pacientes diabéticos como mais susceptíveis a infecções e complicações decorrentes destas. Paracoccidioidomicose (PCM) é uma enfermidade sistêmica causada por fungos da espécie Paracoccidioides sp., bastante importante no Brasil e endêmica em toda a América Latina. Este trabalho utiliza um modelo de carência relativa de insulina (DM experimental) para estudar a intervenção da insulina em um modelo de micose pulmonar causada por P. brasiliensis, analisando o processo de migração celular (expressão de moléculas de adesão por imunohistoquímica e fenótipo dos leucócitos do pulmão por citometria de fluxo), os mecanismos moleculares (produção/liberação de citocinas por cytometric bead array), intracelulares (vias de sinalização por Western blot), e a atividade fagocítica e microbicida dos macrófagos alveolares. Em resultados observamos que, comparados aos não-diabéticos, camundongos tornados diabéticos apresentam maior susceptibilidade evidenciada por menor atividade fagocítica e reduzidas secreções de interferon-γ e de interleucina-12 na fase inicial da inflamação, que leva a uma resposta menos efetiva com menor expressão de molécula de adesão de células vasculares, reduzidas populações de linfócitos TCD4+, TCD8+, células natural killer, culminando em inflamação crônica resultante da proliferação aumentada do fungo nos pulmões (aumento de interferon-γ e fator necrótico tumoral-ß). Vemos ainda que o tratamento de insulina em animais diabéticos restaurou as secreções de citocinas pró-inflamatórias e a atividade fagocítica de macrófagos em 24 horas de infecção, e aumentou a celularidade, a expressão de moléculas de adesão de células vasculares-1 e restaurou as populações de linfócitos B, de células natural killer e de células coestimuladas por CD80, além de reduzir a inflamação crônica no pulmão. Estes dados em conjunto nos permitem inferir que a insulina modulou o ambiente inflamatório de animais tornados diabéticos de formas diferentes em estágios iniciais e tardios da infecção pelo isolado Pb18 do Paracoccidioides brasiliensis

Diabetes mellitus comprehends a group of metabolic diseases of great importance and incidence worldwide. Type 1 diabetes mellitus is characterized by destruction of insulin producing-pancreatic cells and, among its symptoms, an impaired immunological function has been observed in many studies having diabetic patients described as more susceptible to infections and complications resulted of them. Paracoccidioidomycosis is a systemic disease caused by fungi of Paracoccidioides spp. , also of great importance in Brazil and endemic in the whole Latin America. This work uses a model of experimental T1DM to investigate the intervention of insulin in a model of murine PCM induced by Paracoccidioides brasiliensis, analyzing the process of cell migration (adhesion molecules expression, leukocyte phenotyping), molecular mechanisms (production and secretion of cytokines), intracellular mechanisms (signaling pathways) and phagocytic and microbicidal activities in alveolar macrophages. In results, compared to controls, we observed higher susceptibility in diabetic mice to PCM, evidenced by reduced phagocytic activity and reduced levels of interferon-γ and interleukin-12 on initial stages of infection, and a less effective inflammation with lesser expression of adhesion molecules, reduced migration of TCD4+, TCD8+, NK cells and B lymphocytes, resulting in chronic inflammation caused by higher fungal proliferation in lungs (higher interferon-γ and tumours necrosis factor-α levels). In addition, we saw treatment with insulin in diabetic animals restored secretion of pro-inflammatory cytokines and phagocytic activity on early stages and allowed higher cellularity, higher expression of vascular cells adhesion molecule-1 and restored populations of B lymphocytes, NK cells and the expression of costimularoty molecule CD80, also reducing the chronic inflammation in lungs. Taken together, these data lead us to suggest insulin modulated the inflammatory microenvironment in lungs of mice rendered diabetic, in different forms on earlier and later stages of an infection by Pb18 isolate

Sleep quality and architecture in COPD: the relationship with lung function abnormalities / Qualidade e arquitetura do sono na DPOC: relação com anormalidades da função pulmonar

ABSTRACT Objective: Impaired respiratory mechanics and gas exchange may contribute to sleep disturbance in patients with COPD. We aimed to assess putative associations of different domains of lung function (airflow limitation, lung volumes, and gas exchange efficiency) with polysomnography (PSG)-derived parameters of sleep quality and architecture in COPD. Methods: We retrospectively assessed data from COPD 181 patients ≥ 40 years of age who underwent spirometry, plethysmography, and overnight PSG. Univariate and multivariate linear regression models predicted sleep efficiency (total sleep time/total recording time) and other PSG-derived parameters that reflect sleep quality. Results: The severity of COPD was widely distributed in the sample (post-bronchodilator FEV1 ranging from 25% to 128% of predicted): mild COPD (40.3%), moderate COPD (43.1%), and severe-very severe COPD (16.6%). PSG unveiled a high proportion of obstructive sleep apnea (64.1%) and significant nocturnal desaturation (mean pulse oximetry nadir = 82.2% ± 6.9%). After controlling for age, sex, BMI, apnea-hypopnea index, nocturnal desaturation, comorbidities, and psychotropic drug prescription, FEV1/FVC was associated with sleep efficiency (β = 25.366; R2 = 14%; p < 0.001), whereas DLCO predicted sleep onset latency (β = −0.314; R2 = 13%; p < 0.001) and rapid eye movement sleep time/total sleep time in % (β = 0.085; R2 = 15%; p = 0.001). Conclusions: Pulmonary function variables reflecting severity of airflow and gas exchange impairment, adjusted for some potential confounders, were weakly related to PSG outcomes in COPD patients. The direct contribution of the pathophysiological hallmarks of COPD to objectively measured parameters of sleep quality seems to be less important than it was previously assumed.

RESUMO Objetivo: O comprometimento da mecânica respiratória e das trocas gasosas pode contribuir para distúrbios do sono em pacientes com DPOC. Objetivamos avaliar associações putativas de diferentes domínios da função pulmonar (limitação do fluxo aéreo, volumes pulmonares e eficiência das trocas gasosas) com parâmetros da qualidade e arquitetura do sono na DPOC derivados da polissonografia (PSG). Métodos: Avaliamos retrospectivamente dados de 181 pacientes com DPOC e idade ≥ 40 anos que foram submetidos a espirometria, pletismografia e PSG de noite inteira. Modelos de regressão linear univariada e multivariada foram utilizados para avaliar a associação de variáveis de função pulmonar com a eficiência do sono (tempo total de sono/tempo total de registro) e outros parâmetros derivados da PSG que refletem a qualidade do sono. Resultados: A gravidade da DPOC foi bem distribuída na amostra (VEF1 pós-broncodilatador variando de 25% a 128% do previsto): DPOC leve (40,3%), DPOC moderada (43,1%) e DPOC grave-muito grave (16,6%). A PSG revelou uma alta frequência de apneia obstrutiva do sono (64,1%) e dessaturação noturna significativa (nadir médio da oximetria de pulso = 82,2% ± 6,9%). Após controle para idade, sexo, IMC, índice de apneia-hipopneia, dessaturação noturna, comorbidades e prescrição de psicotrópicos, a relação VEF1/CVF apresentou associação com a eficiência do sono (β = 25,366; R2 = 14%; p < 0,001), enquanto a DLCO previu a latência para o início do sono (β = −0,314; R2 = 13%; p < 0,001) e o tempo de sono rapid eye movement/tempo total de sono em % (β = 0,085; R2 = 15%; p = 0,001). Conclusões: As variáveis de função pulmonar que refletem a gravidade do comprometimento do fluxo aéreo e das trocas gasosas, ajustadas para alguns potenciais fatores de confusão, apresentaram fraca relação com os resultados da PSG nos pacientes com DPOC. A contribuição direta das características fisiopatológicas da DPOC para os parâmetros da qualidade do sono medidos objetivamente parece ser menos importante do que se supunha anteriormente.

Necrosis pulmonar masiva por micosis / Massive pulmonary necrosis due to mycosis

Introducción: La aspergilosis es una infección micótica oportunista que se presenta fundamentalmente en pacientes inmunodeprimidos y su principal fuente de transmisión lo constituyen las esporas presentes en el aire de salones de operaciones y unidades de cuidados intensivos. Objetivo: Presentar un caso de una micosis pulmonar masiva por una variante angioinvasiva de Aspergillus. Caso clínico: Se presenta un paciente con aspergilosis pulmonar grave, diagnosticada después de la resección de un tumor mediastinal. Se describen las características de la primera intervención, la evolución postoperatoria que condujo a la segunda, se muestran las imágenes tomográficas, quirúrgicas, microbiológicas y anátomo-patológicas que permitieron definir el diagnóstico. Conclusiones: La posibilidad de una micosis pulmonar debe tenerse en cuenta, aun cuando sea una afección rara y de manejo difícil, en pacientes inmunodeprimidos, con condensación pulmonar rebelde al tratamiento(AU)

Introduction: Aspergillosis is an opportunistic fungal infection that occurs mainly in immunosuppressed patients and its main source of transmission is the spores present in the air of operating rooms and intensive care units. Objective: To present a case of a massive pulmonary mycosis due to an angioinvasive variant of Aspergillus. Clinical case: A patient with severe pulmonary aspergillosis, diagnosed after resection of a mediastinal tumor, is presented. The characteristics of the first intervention are described, the postoperative evolution that led to the second one, the tomographic, surgical, microbiological and anatomo-pathological images that allowed to define the diagnosis are shown. Conclusions: The possibility of a pulmonary mycosis should be taken into account, even when it is a rare and difficult-to-handle condition, in immunocompromised patients, with pulmonary condensation that is rebellious to treatment. Aspergillosis is an opportunistic fungal infection that occurs mainly in immunosuppressed patients and its main source of transmission is the spores present in the air of operating rooms and intensive care units(AU)

Infusion of convalescent plasma is associated with clinical improvement in critically ill patients with Covid-19: a pilot study

ABSTRACT Background: The ideal treatment of coronavirus disease (COVID)-19 has yet to be defined, but convalescent plasma (CoPla) has been successfully employed. Objective: The objective of the study was to study the safety and outcomes of the administration of CoPla to individuals with severe COVID-19 in an academic medical center. Methods: Ten patients were prospectively treated with plasma from COVID-19 convalescent donors. Results: Over 8 days, the sequential organ failure assessment score dropped significantly in all patients, from 3 to 1.5 (p = 0.014); the Kirby index (PaO2/FiO2) score increased from 124 to 255, (p < 0.0001), body temperature decreased significantly from 38.1 to 36.9°C (p = 0.0058), and ferritin levels also dropped significantly from 1736.6 to 1061.8 ng/ml (p = 0.0001). Chest X-rays improved in 7/10 cases and in 6/10, computerized tomography scans also revealed improvement of the lung injury. Decreases in C-reactive protein and D-dimer levels were also observed. Three of five patients on mechanical ventilation support could be extubated, nine were transferred to conventional hospital floors, and six were sent home; two patients died. The administration of CoPla had no side effects and the 24-day overall survival was 77%. Conclusions: Although other treatments were also administered to the patients and as a result data are difficult to interpret, it seems that the addition of CoPla improved pulmonary function.

Cavidades pulmonares en Lupus Eritematoso Sistémico / Lung cavities in Systemic Lupus Erythematosus

Las lesiones pulmonares cavitadas en pacientes con Lupus Eritematoso Sistémico (LES) han sido descriptas en asociación con neumonitis por citomegalovirus, o secundarias a infecciones fúngicas. Haciendo una revisión en la literatura, se han descripto 13 casos de pacientes con estas lesiones. Presentamos cuatro pacientes con diagnóstico de LES, que durante la evolución de su enfermedad desarrollan cavidades pulmonares.

Cavitary lung lesions in patients with SLE have been described in association with cytomegalovirus pneumonitis, or secondary to fungal infections. Making a review in the literature, 13 cases of patients with these lesions have been described. We present four patients diagnosed with SLE, whom developed lung cavities during the evolution of the disease.

Lung cavities in chronic thromboembolic pulmonary hypertension

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a unique form of pulmonary hypertension (PH) that arises from obstruction of the pulmonary vessels by recanalized thromboembolic material. CTEPH has a wide range of radiologic presentations. Commonly, it presents as main pulmonary artery enlargement, peripheral vascular obstructions, bronchial artery dilations, and mosaic attenuation patterns. Nevertheless, other uncommon presentations have been described, such as lung cavities. These lesions may be solely related to chronic lung parenchyma ischemia but may also be a consequence of concomitant chronic infectious conditions. The objective of this study was to evaluate the different etiologies that cause lung cavities in CTEPH patients. METHODS: A retrospective data analysis of the medical records of CTEPH patients in a single reference PH center that contained or mentioned lung cavities was conducted between 2013 and 2016. RESULTS: Seven CTEPH patients with lung cavities were identified. The cavities had different sizes, locations, and wall thicknesses. In two patients, the cavities were attributed to pulmonary infarction; in 5 patients, an infectious etiology was identified. CONCLUSION: Despite the possibility of being solely associated with chronic lung parenchyma ischemia, most cases of lung cavities in CTEPH patients were associated with chronic granulomatous diseases, reinforcing the need for active investigation of infectious agents in this setting.

Symptom variability over the course of the day in patients with stable COPD in Brazil: a real-world observational study / Variabilidade dos sintomas diários de pacientes com DPOC estável no Brasil: um estudo observacional de vida real

ABSTRACT Objective: To analyze symptoms at different times of day in patients with COPD. Methods: This was a multicenter, cross-sectional observational study conducted at eight centers in Brazil. We evaluated morning, daytime, and nighttime symptoms in patients with stable COPD. Results: We included 593 patients under regular treatment, of whom 309 (52.1%) were male and 92 (15.5%) were active smokers. The mean age was 67.7 years, and the mean FEV1 was 49.4% of the predicted value. In comparison with the patients who had mild or moderate symptoms, the 183 (30.8%) with severe symptoms were less physically active (p = 0.002), had greater airflow limitation (p < 0.001), had more outpatient exacerbations (p = 0.002) and more inpatient exacerbations (p = 0.043), as well as scoring worse on specific instruments. The most common morning and nighttime symptoms were dyspnea (in 45.2% and 33.1%, respectively), cough (in 37.5% and 33.3%, respectively), and wheezing (in 24.4% and 27.0%, respectively). The intensity of daytime symptoms correlated strongly with that of morning symptoms (r = 0.65, p < 0.001) and that of nighttime symptoms (r = 0.60, p < 0.001), as well as with the COPD Assessment Test score (r = 0.62; p < 0.001), although it showed only a weak correlation with FEV1 (r = −0.205; p < 0.001). Conclusions: Dyspnea was more common in the morning than at night. Having morning or nighttime symptoms was associated with greater daytime symptom severity. Symptom intensity was strongly associated with poor quality of life and with the frequency of exacerbations, although it was weakly associated with airflow limitation.

RESUMO Objetivo: Analisar os sintomas em diferentes momentos do dia em pacientes com DPOC. Métodos: Estudo observacional multicêntrico de corte transversal em oito centros brasileiros. Foram avaliados os sintomas matinais, diurnos e noturnos em pacientes com DPOC estável. Resultados: Foram incluídos 593 pacientes em tratamento regular, sendo 309 (52,1%) do sexo masculino e 92 (15,5%) fumantes ativos. A média de idade foi de 67,7 anos, e a média de VEF1 foi de 49,4% do valor previsto. Os pacientes com sintomas mais graves (n = 183; 30,8%), em comparação com aqueles com sintomas leves e moderados, apresentaram pior nível de atividade física (p = 0,002), maior limitação ao fluxo aéreo (p < 0,001), exacerbações ambulatoriais (p = 0,002) e hospitalares (p = 0,043) mais frequentemente e piores resultados em instrumentos específicos. Os sintomas matinais e noturnos mais frequentes foram dispneia (em 45,2% e 33,1%, respectivamente), tosse (em 37,5% e 33,3%, respectivamente) e chiado (em 24,4% e 27,0%, respectivamente). Houve forte correlação da intensidade dos sintomas diurnos com sintomas matinais (r = 0,65, p < 0,001), sintomas noturnos (r = 0,60, p < 0,001), bem como com o escore do COPD Assessment Test (r = 0,62; p < 0,001); porém, houve uma correlação fraca com VEF1 (r = −0,205; p < 0,001). Conclusões: A dispneia foi mais frequente no período matinal do que no período noturno. Ter sintomas matinais e/ou noturnos foi associado à pior gravidade dos sintomas diurnos. A intensidade dos sintomas foi fortemente associada a pior qualidade de vida e frequência de exacerbações, mas fracamente associada à limitação ao fluxo aéreo.

Padrões de tomografia computadorizada de alta resolução na doença pulmonar intersticial (DPI): prevalência e prognóstico / High resolution computed tomography patterns in interstitial lung disease (ILD): prevalence and prognosis

RESUMO Objetivo Correlacionar a prevalência e o prognóstico de cada padrão de TCAR de pneumonia intersticial usual (PIU) típica, provável e indeterminada com o diagnóstico clínico multidisciplinar de doença pulmonar intersticial (DPI). Métodos Incluímos todos os pacientes com diagnóstico multidisciplinar de DPI com padrão de TCAR de PIU típica, PIU provável ou indeterminada para PIU. Dados clínicos e histopatológicos, teste de função pulmonar e status de sobrevida foram obtidos retrospectivamente. O diagnóstico final foi validado por uma equipe multidisciplinar. Resultados Foram incluídos no estudo 244 pacientes, com média de idade de 68 ± 13 anos sendo 52,5% do sexo masculino. Em um total de 106 pacientes com padrão típico de PIU, 62% tiveram o diagnóstico multidisciplinar de FPI, 20% de pneumonia por hipersensibilidade crônica (PHC) e 10% de DPI relacionada à doença do tecido conjuntivo (DPI-DTC). Dos 114 casos com provável PIU, DPI-DTC correspondeu a 39%, FPI a 31%, pneumonia intersticial descamativa a 11%, doença pulmonar relacionada a medicamentos a 9% e PHC a 8%. Nos 24 pacientes com TC indeterminada para PIU, o DPI-DTC foi o diagnóstico final em 33%, seguido por pneumonia intersticial descamativa (21%) e FPI (13%). Pacientes com PIU típica apresentaram maior probabilidade de morrer ou realizar transplante de pulmão no seguimento (17,9% e 11,3%, respectivamente). Conclusões FPI, PHC e DPI-DTC foram os principais diagnósticos diferenciais em pacientes com padrão de TCAR de PIU típica, provável e indeterminada. Pacientes com padrão de PIU típico na TCAR tiveram maior probabilidade de morrer ou realizar transplante de pulmão no seguimento.

ABSTRACT Objective To correlate the prevalence and prognosis of each HRCT pattern of typical, probable, and indeterminate usual interstitial pneumonia (UIP) with the clinical multidisciplinary diagnosis of interstitial lung disease (ILD). Methods We included all patients with a multidisciplinary diagnosis of ILD with an HRCT pattern of typical UIP, probable UIP, or indeterminate for UIP. Clinical and histopathological data, pulmonary function tests, and survival status were retrospectively obtained. The final diagnosis was validated by a multidisciplinary team. Results A total of 244 patients were included in the study, with a mean age of 68 ±13 years and being 52.5% males. In a total of 106 patients with typical UIP pattern, 62% had the multidisciplinary diagnosis of IPF, 20% had chronic hypersensitivity pneumonitis (CHP), and 10% had connective tissue disease-related ILD (CTD-ILD). Out of the 114 cases with probable UIP, CTD-ILD corresponded to 39%, IPF to 31%, desquamative interstitial pneumonia to 11%, drug-related lung disease to 9%, and CHP to 8%. In the 24 patients with CT indeterminate for UIP, CTD-ILD was the final diagnosis in 33%, followed by desquamative interstitial pneumonia (21%), and IPF (13%). Patients with typical UIP were more likely to die or had lung transplantation in the follow-up (17.9% and 11.3%, respectively). Conclusion IPF, CHP, and CTD-ILD were the main differential diagnoses in patients with HRCT patterns of typical, probable and indeterminate UIP. Patients with HRCT typical UIP pattern were more likely to die or had lung transplantation in the follow-up.

Transplante pulmonar em pacientes com fibrose pulmonar familiar / Lung transplant in patients with familial pulmonary fibrosis

RESUMO Objetivo A fibrose pulmonar familiar (FPF) é definida como uma doença pulmonar intersticial idiopática que afeta dois ou mais membros da mesma família. Nesses pacientes, os resultados têm sido insatisfatórios, apresentando alto risco de morte e disfunção crônica do enxerto pulmonar (CLAD) após o transplante de pulmão. O objetivo do presente estudo foi comparar o resultado de curto e longo prazo do transplante de pulmão em pacientes com FPF e pacientes transplantados por outras doenças pulmonares intersticiais. Métodos Foram coletados retrospectivamente dados clínicos pré e pós-transplante de 83 pacientes com fibrose pulmonar submetidos a transplante de pulmão. Os pacientes foram divididos em aqueles com fibrose pulmonar familiar (n = 9, grupo FPF) e aqueles com fibrose pulmonar não familiar (n = 74, grupo controle). Resultados O grupo FPF foi composto de quatro mulheres e cinco homens, sendo 44,5% ex-fumantes. A maioria apresentou tomografia computadorizada e evidência patológica de pneumonia intersticial usual. Os pacientes com FPF tiveram níveis significativamente menores de hemoglobina e hematócrito. Não foram observadas outras diferenças nas características pré e pós-transplante em relação ao grupo controle. A evolução clínica pós-operatória foi semelhante nos dois grupos. Não foi constatada diferença significativa na sobrevida de um ano livre de CLAD e na sobrevida em geral. Conclusão A evolução pós-transplante de pacientes com FPF foi semelhante à dos pacientes com fibrose pulmonar não familiar, embora mais pacientes com FPF tivessem anemia pré-transplante. O resultado a curto e longo prazo foi comparável em ambos os grupos. O transplante de pulmão provou ser uma opção válida para pacientes com FPF, assim como para pacientes com outros tipos de fibrose pulmonar.

ABSTRACT Objective Familial pulmonary fibrosis (FPF) is defined as an idiopathic interstitial lung disease affecting two or more members of the same family; poor outcome with high risk of death and chronic lung allograft dysfunction (CLAD) after lung transplant has been reported in these patients. The present study aimed to compare the short- and long-term outcome of lung transplants in patients with FPF and patients transplanted because of other interstitial lung diseases. Method Clinical pre- and post-transplant data from 83 consecutive patients with pulmonary fibrosis who underwent lung transplant at our centre were collected retrospectively. Patients were divided into those with familial (n=9 FPF group) and those with non-familial pulmonary fibrosis (n=74 controls). Results The FPF group was composed of 4 females and 5 males; 44.5% were ex-smokers. The majority presented their CT scan and pathology evidence of usual interstitial pneumonia. Patients with FPF had significantly lower pre-transplant levels of haemoglobin and haematocrit. No other differences in pre- and post-transplant characteristics were observed concerning controls. The clinical post-operative course was similar in the two groups. No significant difference in one-year CLAD-free survival and overall survival was observed. Conclusion The post-transplant course of patients with FPF was similar to patients with non-familial pulmonary fibrosis, although more patients with FPF had pre-transplant anaemia. Short- and long-term outcome was comparable in both groups. Lung transplant proved to be a valid option for patients with FPF as it was for patients with other types of pulmonary fibrosis.

Is it possible to reverse frailty in patients with chronic obstructive pulmonary disease?

In recent years, frailty has attracted increasing attention from clinicians and health care workers. The influence of frailty on the elderly, especially those with chronic diseases of the respiratory system, is highly significant. Frailty is particularly more common in patients with chronic obstructive pulmonary disease (COPD). Frailty and COPD share many risk factors and pathophysiological mechanisms. As a comprehensive interventional method for chronic respiratory diseases, pulmonary rehabilitation is an important basic measure for the management of patients with COPD. Frailty in these patients can be reversed using pulmonary rehabilitation by targeting five components of the frailty phenotype at the entry point. The present review discusses the benefits of pulmonary rehabilitation in patients with COPD complicated by frailty and provides a theoretical basis for pulmonary rehabilitation treatment in this population. In addition, the timing of pulmonary rehabilitation is also addressed, with the prefrail stage being the "golden" period. The implementation of pulmonary rehabilitation must vary among individuals, and individualized treatment strategies will help maximize benefits.