Detection of respiratory viruses and expression of inflammatory cytokines in patients with acute exacerbation chronic obstructive pulmonary disease in Mongolia China / Detecção de vírus respiratórios e expressão de citocinas inflamatórias em pacientes com doença pulmonar obstrutiva crônica de exacerbação aguda na Mongólia, China

Chronic obstructive pulmonary disease (COPD) was estimated to be the third cause of global mortality by 2020. Acute exacerbation COPD (AECOPD) is a sudden worsening of COPD symptoms and could be due to virus/bacterial infections and air pollution. Increased expression of inflammatory markers in patients with AECOPD is associated with viral infection. This study aimed to detect different viruses and analyze the expression of various inflammatory markers associated with AECOPD patients. Three hundred and forty-seven patients diagnosed with COPD according to GOLD criteria were included in this study. Swab samples and blood were collected for the detection of viruses by RT-PCR and expression of inflammatory markers, respectively. Of the swab samples, 113 (32.6%) of samples were positive for virus detection. Of these, HRV (39.8%) was the predominant virus detected followed by FluB (27.4%) and FluA (22.1%). The presence of HRV was significantly higher (p=0.044) among the other detected viruses. When compared to healthy controls the expression levels of TNF-α, IL-6 and IL-8 were significantly higher (p<0.05) in virus-positive patients. The IL-6 and IL-8 were the next predominantly expressed in markers among the samples. The higher expression rate of IL-8 was significantly (p<0.05) associated with patients having COPD GOLD III severity level and smoking history. Although HRV was the predominant virus detected the combined prevalence of Influenza A and B surpassing the rate of HRV. The high-level expression of well known inflammatory markers of AECOPD, TNF-α, IL-6 and IL-8 indicates a chronic severe illness. These markers play an important role and could be used as a marker for determining the severity of AECOPD.

Estima-se que a doença pulmonar obstrutiva crônica (DPOC) seja a terceira causa de mortalidade global em 2020. A exacerbação aguda DPOC (AECOPD) é um agravamento súbito dos sintomas da DPOC e pode ser devido a infecções por vírus/bactérias e poluição do ar. O aumento da expressão de marcadores inflamatórios em pacientes com AECOPD está associado à infecção viral. Este estudo teve como objetivo detectar diferentes vírus e analisar a expressão de vários marcadores inflamatórios associados a pacientes com AECOPD. Trezentos e quarenta e sete pacientes com diagnóstico de DPOC de acordo com os critérios GOLD foram incluídos neste estudo. Amostras de swab e sangue foram coletadas para detecção de vírus por RT-PCR e expressão de marcadores inflamatórios, respectivamente. Das amostras de esfregaço, 113 (32,6%) amostras foram positivas para detecção de vírus. Nestas, o HRV (39,8%) foi o vírus predominante detectado, seguido do FluB (27,4%) e do FluA (22,1%). A presença de VFC foi significativamente maior (p = 0,044) entre os demais vírus detectados. Quando comparados a controles saudáveis, os níveis de expressão de TNF-α, IL-6 e IL-8 foram significativamente maiores (p <0,05) em pacientes com vírus positivo. A IL-6 e a IL-8 foram as próximas predominantemente expressas em marcadores entre as amostras. A maior taxa de expressão de IL-8 foi significativamente (p <0,05) associada a pacientes com grau de gravidade GOLD III da DPOC e história de tabagismo. Embora o HRV tenha sido o vírus predominante, a prevalência combinada de Influenza A e B ultrapassou a taxa de HRV. O alto nível de expressão de marcadores inflamatórios bem conhecidos de AECOPD, TNF-α, IL-6 e IL-8 indica uma doença crônica grave. Esses marcadores desempenham um papel importante e podem ser usados como um marcador para determinar a gravidade da AECOPD.

Acute exacerbations of chronic obstructive pulmonary disease causes and impacts.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are recognised clinically as episodes of increased breathlessness and productive cough requiring a more intensive treatment. A subset of patients with this disease is especially prone to such exacerbations. These patients are labelled as ‘frequent exacerbators’. Though yet poorly characterised in terms of host characteristics, including any genetic basis, these patients are believed to represent a distinct phenotype as they have a different natural history with a more progressive disease and a poorer prognosis than those who get exacerbations infrequently. Most exacerbations appear to be associated with infective triggers, either bacterial or viral, although ‘non-infective’ agents, such as air pollution and other irritants may also be important. Susceptibility to exacerbations is determined by multiple factors. Several risk factors have been identified, some of which are modifiable. Chronic obstructive pulmonary disease (COPD) exacerbations are major drivers of health status and patient-centered outcomes, and are a major reason for health care utilisation including hospitalisations and intensive care admissions. These are associated with considerable morbidity and mortality, both immediate and long-term. These episodes have a negative impact on the patient and the disease including high economic burden, increased mortality, worsening of health status, limitation of activity, and aggravation of comorbidities including cardiovascular disease, osteoporosis and neuro-psychiatric complications. Exacerbations also increase the rate of progression of disease, increasing the annual decline in lung function and leading to a poorer prognosis. Evaluation of risk of exacerbations is now included as a major component of the initial assessment of a patient with COPD in addition to the traditionally used lung function parameter, forced expiratory volume in one second (FEV1). Decreasing the risk of exacerbations and their prevention is a major therapeutic goal of management in COPD.

Consenso Intersociedades para el manejo de infecciones respiratorias: bronquitis aguda y enfermedad pulmonar obstructiva crónica / [Inter-society consensus for the management of respiratory infections: acute bronchitis and chronic obstructive pulmonary disease].

The Argentine Society for Infectious Diseases and other national societies issued updated practical guidelines for the management of acute bronchitis (AB) and reactivations of chronic obstructive pulmonary disease (COPD) with the aim of promoting rational use of diagnostic and therapeutic resources. AB is a condition characterized by inflammation of the bronchial airways which affects adults and children without underlying pulmonary disease. It is usually caused by a virus. The diagnosis is based on clinical findings after community acquired pneumonia has been ruled out. Treatment of AB is mainly symptomatic. Antibiotics should be used in immune-compromised hosts, patients with chronic respiratory or cardiac diseases and in the elderly with co-morbidities. Reactivation of COPD is defined as an acute change in the patient’s baseline clinical situation beyond normal day to day variations, with an increase in dyspnea, sputum production and/or sputum purulence, warranting a change in medication. An increase in one symptom is considered a mild exacerbation, two as moderate, and the presence of three symptoms is considered a severe exacerbation. An infectious agent can be isolated in sputum in 50 to 75

of COPD reactivations. Moderate and severe episodes must be treated with antibiotics, amoxicillin/ beta-lactamase inhibitor, macrolides and fluoroquinolones are first choice drugs.

Etiología y biomarcadores de inflamación sistémica en las exacerbaciones leves a moderadas de la enfermedad pulmonar obstructiva crónica / Etiology and biomarkers of systemic inflammation in mild to moderate COPD exacerbations

Background: The etiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Inflammation increases during exacerbation of COPD. The identification of inflammatory changes will increase our knowledge and potentially guide therapy. Aim: To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and viral exacerbations. Material and Methods: In 85 COPD patients (45 males, mean age 68 ± 8 years, FEV1 46 ± 17% of predicted) sputum, nasopharyngeal swabs and blood samples were collected to identify the causative organism, during a mild to moderate exacerbation. Serum ultrasensitive C reactive protein (CRP), fibrinogen and interleukin 6 (IL 6), neutrophil and leukocyte counts were measured in stable conditions, during a COPD exacerbation, 15 and 30 days post exacerbation. Results: A total of 120 mild to moderate COPD exacerbations were included. In 74 (61.7%), a microbial etiology could be identified, most commonly Mycoplasma pneumoniae (15.8%), Rhinovirus (15%), Haemophilus influenzae (14.2%), Chlamydia pneumoniae (11.7%), Streptococcus pneumoniae (5.8%) and Gram negative bacilli (5.8%). Serum CRP, fibrinogen and IL 6, and neutrophil and leukocyte counts significantly increased during exacerbation and recovered at 30 days post exacerbation. Compared to viral exacerbations, bacterial aggravations were associated with a systemic inflammation of higher magnitude. Conclusions: Biomarkers of systemic inflammation increase during mild to moderate COPD exacerbations. The increase in systemic inflammation seems to be limited to exacerbations caused by bacterial infections.

Helicobacter pylori in patients suffering from pulmonary disease

Recently, research of indirect evidence suggested a possible association between Helicobacter pylori and pulmonary disease. This study aimed to determine if H. pylori could be detected in endobronchial specimens collected from patients undergoing bronchoscopy. This prospective study was conducted on 34 consecutive patients with any type of lung disease undergoing bronchoscopy in which biopsy was required for their diagnosis. A written informed consent was obtained from all participants. Three bronchial mucosa biopsy samples were obtained using fenestrated biopsy forceps. One sample was used to determine urease activity, the second one for histopathological examination, and the third one for diagnosis. All subjects were fully informed regarding the gastroesophageal reflux disorder [GERD] Questionnaire. There were 34 patients with pulmonary diseases [12 males and 22 females, mean age 58.2 +/- 18.2 years] out of which, 11 [32.4%] had GERD. No significant difference was found between the histopathological assay and GERD. Our study found no direct evidence supporting the theory that H. pylori may cause pulmonary disease and no relation with GERD was detected. However, a possible indirect role could not be excluded. Further studies in patients with GERD and lung disease may reveal a potential pathogenic link between H. pylori and pulmonary disease

La aspergilosis pulmonar invasiva en la enfermedad pulmonar obstructiva crónica / Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Invasive pulmonary aspergillosis (IPA) is a severe disease, specially among immunocompromised patients. Its frequency increases in other patients such as those with Chronic Obstructive Pulmonary Disease (COPD), mainly when steroids are prescribed. The most common form of presentation is a respiratory tract infection with poor response to antimicrobial treatment. The delay in its diagnosis is one of the main causes of its high lethality. Once suspected, respiratory secretion cultures, chest X ray examination and computed tomography should be obtained and galactomannan, a marker of hematogenous dissemination of the microorganism, should be determined. Although the repeated isolation of Aspergillus spp is suggestive of invasive disease, the definitive diagnosis requires cytopathological confirmation. Further studies should be performed in these patients, since the available information was obtained from the observations made in immunocompromised patients, and may not be applicable accurately to API among COPD patients.

Comparação entre a azitromicina e a amoxicilina no tratamento da exacerbação infecciosa da doença pulmonar obstrutiva crônica / Comparison between azithromycin and amoxicillin in the treatment of infectious exacerbation of chronic obstructive pulmonary disease

OBJETIVO: Comparar a eficácia, segurança e tolerabilidade da azitromicina e da amoxicilina no tratamento de pacientes com quadro clínico de exacerbação infecciosa da doença pulmonar obstrutiva crônica. MÉTODOS: Seis centros brasileiros incluíram 109 pacientes com idades entre 33 e 82 anos. Desses pacientes, 102 foram randomizados para receber azitromicina (500 mg por dia por três dias, n = 49) ou amoxicilina (500 mg a cada oito horas por dez dias, n = 53). Os pacientes foram avaliados no início do estudo, após dez dias e depois de um mês. A avaliação clínica, de acordo com os sinais e sintomas presentes após dez dias e após um mês, consistiu na classificação dos casos nas categorias cura, melhora ou falha terapêutica. A avaliação microbiológica foi feita pela cultura de amostras de escarro consideradas adequadas após contagem de leucócitos e coloração de Gram. Avaliações secundárias de eficácia foram feitas com relação aos sintomas (tosse, dispnéia e expectoração) e à função pulmonar. RESULTADOS: Não houve diferenças entre as proporções de casos classificados como cura ou melhora entre os grupos tratados com a azitromicina ou a amoxicilina. Essas proporções foram, respectivamente, de 85 por cento vs. 78 por cento (p = 0,368) após dez dias, e de 83 por cento vs. 78 por cento (p = 0,571) após um mês. Também não foram encontradas diferenças significativas entre os dois grupos quando comparadas as variáveis secundárias de eficácia e a incidência de eventos adversos. CONCLUSÃO: A azitromicina tem eficácia e tolerabilidade semelhantes às da amoxicilina para o tratamento da exacerbação aguda da Doença pulmonar obstrutiva crônica.

OBJECTIVE: To compare the efficacy, safety, and tolerability of azithromycin and amoxicillin in the treatment of patients with infectious exacerbation of chronic obstructive pulmonary disease. METHODS: This study was conducted at six medical centers across Brazil and included 109 patients from 33 to 82 years of age. Of those, 102 were randomized to receive either azithromycin (500 mg/day for three days, n = 49) or amoxicillin (500 mg every eight hours for ten days, n = 53). The patients were evaluated at the study outset, on day ten, and at one month. Based on the clinical evaluation of the signs and symptoms present on day ten and at one month, the outcomes were classified as cure, improvement, or treatment failure. The microbiological evaluation was made through the culture of sputum samples that were considered appropriate samples only after leukocyte counts and Gram staining. Secondary efficacy evaluations were made in order to analyze symptoms (cough, dyspnea, and expectoration) and pulmonary function. RESULTS: There were no differences between the groups treated with azithromycin or amoxicillin in terms of the percentages of cases in which the outcomes were classified as cure or improvement: 85 percent vs. 78 percent (p = 0.368) on day ten; and 83 percent vs. 78 percent (p = 0.571) at one month. Similarly, there were no significant differences between the two groups in the secondary efficacy variables or the incidence of adverse effects. CONCLUSION: Azithromycin and amoxicillin present similar efficacy and tolerability in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Seroprevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in Stable Asthma and Chronic Obstructive Pulmonary Disease

Mycoplasma pneumoniae and Chlamydia pneumoniae have been suggested to take part in the acute exacerbation of bronchial asthma and chronic obstructive pulmonary disease (COPD). Several studies have questioned whether they may play pathogenic roles in connection with bronchial asthma and COPD. This study was designed to evaluate the seroprevalences of M. pneumoniae and C. pneumoniae in stable asthma and COPD patients, and to compare with control patients. The medical records of one hundred forty patients who underwent M. pneumoniae and C. pneumoniae serology were retrospectively reviewed. Seroprevalences of M. pneumoniae and C. pneumoniae in the asthma group (11.1% and 8.3%, respectively) were higher than in the control group (4.4% and 2.2%, respectively) without statistical significance. The seroprevalence of M. pneumoniae in the COPD group (16.9%) was significantly higher than in the control group, and the seroprevalence of C. pneumoniae in the COPD group (3.4%) was higher than in the control group without statistical significance. This study raises important questions about the relation of M. pneumoniae and C. pneumoniae infection with stable asthma or COPD.