Viral infections in obstructive airway diseases

The most common syndromes associated with obstructive lung disease are asthma and chronic obstructive pulmonary disease (COPD). Evidence for a viral etiology of asthmatic exacerbations is well known, but evidence for a role for viruses in COPD exacerbation is just emerging. Viruses may cause chronic infection in both diseases. This paper reviews some studies on the effects of respiratory viruses on asthma and COPD published in 2002 and discusses their relevance to current thinking in pulmonary medicine.     

Virus and Mycoplasma pneumoniae prevalence in a selected pediatric population with acute asthma exacerbation

Objective: To determine the prevalence of viral and atypical bacteria Mycoplasma pneumoniae infection in children experiencing asthma exacerbation and compare positive and negative subjects with regard to exacerbation severity, need for hospitalization, and treatment. Methods: One hundred sixty-nine asthmatic children aged 2–15 years old who were admitted to emergency rooms in Bogota, Colombia for acute asthma exacerbation were interviewed. Nasopharyngeal aspirates were taken for DNA and RNA extraction. M. pneumoniae and virus were detected by PCR using specific primers. Results: The prevalence of M. pneumoniae and viral infection in the study population was 12.4% and 83.7%, respectively. All subjects positive for M. pneumoniae were also positive for viral infection. Rhinovirus was the most frequently detected viral agent. No significant differences in severity of asthma exacerbations or in need for hospitalization between the virus or M. pneumoniae positive and negative groups were observed. A significantly lower percentage of M. pneumoniae positive subjects had used inhaled steroids over the six months prior to asthma exacerbation compared to M. pneumoniae negative subjects (38.1% vs. 68.2%), suggesting that inhaled corticosteroids may have a protective effect against M. pneumoniae infections. Conclusions: The M. pneumoniae and virus prevalence found in this study were similar to those described in the literature. The 100% co-infection rate observed suggests that viral infection can predispose patients to M. pneumoniae infection, and that this interaction may trigger asthmatic exacerbation. Further studies should be done to confirm the protective effect of inhaled corticosteroids on M. pneumoniae infection in patients with asthma exacerbations.     

Evaluation of Respiratory Viral Pathogens in Acute Asthma Exacerbations during Childhood

Objective. Common upper respiratory tract viruses are the most frequent and important causes of asthma exacerbations in both children and adults. Prospective epidemiologic studies report that up to 80% of childhood exacerbations are associated with viral upper respiratory tract infections. Materials and methods. The study group consisted of 104 children with asthma aged 3–17 years who received treatment for asthma exacerbations in our clinic between September 2009 and 2010. Nasopharyngeal and nasal swabs were obtained from all patients during an acute attack, and from the control group (31 subjects). These specimens were investigated for the presence of viral respiratory pathogens using a real-time multiplex PCR method. The patients were compared for the presence of respiratory pathogens and factors related to the severity of the asthma exacerbation. Results. A pathogenic respiratory virus was detected in 53.8% of patients in the acute exacerbation group. The most commonly encountered viral agent was Rhinovirus (35.6%). Patients who had an acute exacerbation with or without a detectable viral pathogen were compared according to the severity of the exacerbation, the need for systemic steroids, and hospitalization rates. No statistically significant difference was found. Conclusion. Although viral upper respiratory tract infections are the most common cause of asthma exacerbations, the severity level of the exacerbation seems to be independent of whether a respiratory virus has been detected.     

The role of chemokines in virus-associated asthma exacerbations

Asthma is a chronic disease characterized by mast cell activation, mucus hypersecretion, airway obstruction, influx and activation of eosinophils, and generation of a predominant T-helper type 2-based cytokine environment. In individuals with established asthma, acute exacerbations requiring hospitalization result primarily from pulmonary viral infection, such as with influenza, rhinovirus, or respiratory syncytial virus. The mechanism for viral exacerbation of the asthmatic response is unclear, but evidence points to a key role for chemokines, a class of cytokines that are important in leukocyte recruitment, inflammatory cell activation, and T-cell differentiation. In this review, we focus on the chemokines upregulated in acute viral-induced exacerbation and examine their role in promoting the virus-induced pathophysiologic response in asthmatic individuals.     

The role of viral respiratory infections in the pathogenesis and exacerbation of asthma

Respiratory viral infections are implicated in both the pathogenesis and exacerbation of asthma. Infections with respiratory syncytial virus and parainfluenza virus are the major cause of wheezing-related respiratory infections early in life. Infections in early childhood affect the immune system and modify the risk for subsequent development of allergies and asthma. Later in life, rhinovirus and influenza are implicated frequently in the exacerbation of asthma. The management of respiratory viral infections includes adequate prophylaxis and treatment of acute infections. Insights into the mechanism of viral respiratory tract infections will provide therapeutic targets for treatment and possibly the prevention of virus-induced asthma.     

病毒感染与肺部急性炎症关系的初步研究

目的观察肺部急性炎症与病毒感染的关系。方法采用间接酶联免疫吸附试验(ELISA)方法检测血清流感病毒A(FluA)、流感病毒B(FluB)、呼吸道合胞病毒(RSV)、腺病毒(ADV)和副流感病毒(PIV)的IgM抗体。结果217例肺部急性炎症患者中病毒IgM抗体阳性的患者86例,为39.63%,其中慢性阻塞性肺疾病急性加重患者病毒抗体阳性75例;在所有病毒抗体阳性标本中,共有144例次抗体阳性,其中FluB54例,占37.5%,FluA30例,占20.83%,副流感病毒25例,占17.36%,腺病毒22例,占15.28%,呼吸道合胞病毒13例,占9.03%。结论病毒感染是造成肺部急性炎症的重要原因之一。     

Role of viruses and atypical bacteria in exacerbations of asthma in hospitalized children: a prospective study in the Nord-Pas de Calais region (France)

We studied the role of viruses and atypical bacteria in children hospitalized with exacerbated asthma by a prospective study of children with acute asthma admitted to the Department of Pediatrics in Lille, and to 15 hospitals in the Nord-Pas de Calais region, from October 1, 1998-June 30, 1999. We included children aged 2-16 years with active asthma, defined as three or more recurrent episodes of reversible wheezing. The severity of asthma and of asthmatic exacerbations was recorded. Immunofluorescence assays (IFA) on nasopharyngeal secretions (NPS), serological tests, or both, were used for detection of influenza virus, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and coronavirus. Polymerase chain reaction (PCR) assays on NPS were used for rhinovirus and enterovirus. Serological tests for Chlamydia pneumoniae and Mycoplasma pneumoniae were performed. A control group of asymptomatic asthmatic outpatients was examined for respiratory viruses (using IFA and PCR). Eighty-two symptomatic children (mean age, 7.9 years) were examined. Viruses were detected in 38% (enterovirus, 15.8%; rhinovirus, 12%; RSV, 7.3%). Serological tests for atypical bacteria were positive in 10% of patients (C. pneumoniae, 5%; M. pneumoniae, 5%). Among the 27 control subjects (mean age, 7.9 years), one PCR was positive for enterovirus. There was no correlation between severity of chronic asthma or asthmatic exacerbations and the diagnosis of infection. Atypical bacterial pathogen infections were linked with prolonged asthmatic symptoms. In conclusion, we confirmed the high incidence of viral infection in acute exacerbations of asthma, especially enteroviruses or rhinoviruses. Persistent clinical features were more frequently associated with atypical bacterial infections, suggesting that these infections should be investigated and treated in cases of persistent asthmatic symptoms.     

Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production

Acute exacerbations are the major cause of asthma morbidity, mortality, and health-care costs and are difficult to treat and prevent. The majority of asthma exacerbations are associated with rhinovirus (RV) infection, but evidence supporting a causal relationship is weak and mechanisms are poorly understood. We hypothesized that in asthmatic, but not normal, subjects RV infection would induce clinical, physiologic, and pathologic lower airway responses typical of an asthma exacerbation and that these changes would be related to virus replication and impaired T helper 1 (Th1)/IL-10 or augmented Th2 immune responses. We investigated physiologic, virologic, and immunopathologic responses to experimental RV infection in blood, induced sputum, and bronchial lavage in 10 asthmatic and 15 normal volunteers. RV infection induced significantly greater lower respiratory symptoms and lung function impairment and increases in bronchial hyperreactivity and eosinophilic lower airway inflammation in asthmatic compared with normal subjects. In asthmatic, but not normal, subjects virus load was significantly related to lower respiratory symptoms, bronchial hyperreactivity, and reductions in blood total and CD8⁺ lymphocytes; lung function impairment was significantly related to neutrophilic and eosinophilic lower airway inflammation. The same virologic and clinical outcomes were strongly related to deficient IFN-γ and IL-10 responses and to augmented IL-4, IL-5, and IL-13 responses. This study demonstrates increased RV-induced clinical illness severity in asthmatic compared with normal subjects, provides evidence of strong relationships between virus load, lower airway virus-induced inflammation and asthma exacerbation severity, and indicates augmented Th2 or impaired Th1 or IL-10 immunity are likely important mechanisms.     

Viruses in asthma exacerbations

PURPOSE OF REVIEW: Respiratory viruses are well recognized as major triggers of acute exacerbations of asthma in children and adults, resulting in frequent outpatients visits and hospitalizations. Clinical and epidemiologic evidence supports this association. The application of molecular diagnostic methods has improved understanding of viral epidemiology and the pathophysiological mechanisms involved in viral induced acute asthma. This article reviews publications since October 2002 for an update of the role of viruses in exacerbations of asthma. RECENT FINDINGS: Respiratory viruses are present in most patients hospitalized for life-threatening asthma and acute non life-threatening asthma. Rhinovirus is the most common, but coinfection with other viruses may be important. Patients with asthma are not more susceptible to upper respiratory tract rhinovirus infections than healthy people but suffer from more severe consequences of the lower respiratory tract infection. Recent epidemiologic studies suggest that viruses provoke asthma attacks by additive or synergistic interactions with allergen exposure or with air pollution. An impaired antiviral immunity to rhinovirus may lead to impaired viral clearance and hence prolonged symptoms. Respiratory viral infections cause asthmatic exacerbations by triggering recruitment of Th2-type cells into the lungs. There is no specific antiviral strategy for prevention of respiratory-triggered asthma exacerbations, although clinical trials of potential antiviral agents are ongoing. Indirect prevention strategies focus on the reduction of overall airway inflammation to reduce the severity of the host response to respiratory viral infections. SUMMARY: Respiratory viral infections are a major cause of morbidity and mortality in asthma. There is a lack of specific antiviral strategies in the prevention or reduction of viral-triggered asthma exacerbations. Recent advances in understanding of the epidemiology and immunopathogenesis of respiratory viral infection in asthma provide opportunities or identification of specific targets for antiviral agents and strategies for management and prevention.     

Detection and characterization of respiratory viruses causing acute respiratory illness and asthma exacerbation in children during three different seasons (2011–2014) in Mexico City

Background

Viral infections play a significant role in causing acute respiratory infections (ARIs) and exacerbations of chronic diseases. Acute respiratory infections are now the leading cause of mortality in children worldwide, especially in developing countries. Recently, human rhinovirus (HRV) infection has been emerged as an important cause of pneumonia and asthma exacerbation.

Objectives

To determine the role of several viral agents principally, respiratory syncytial virus, and HRV in children with ARIs and their relationship with asthma exacerbation and pneumonia.

Methods

Between October 2011 and March 2014, 432 nasopharyngeal samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were tested for the presence of respiratory viruses using a multiplex RT-qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections.

Results

Viral infections were detected in at least 59·7% of the enrolled patients, with HRV (26·6%) being the most frequently detected. HRV infections were associated with clinical features of asthma and difficulty in breathing such as wheezing (P = 0·0003), supraesternal (P = 0·046), and xiphoid retraction (P = 0·030). HRV subtype C (HRV-C) infections were associated with asthma (P = 0·02).

Conclusions

Human rhinovirus was the virus most commonly detected in pediatric patients with ARI. There is also an association of HRV-C infection with asthma exacerbation, emphasizing the relevance of this virus in severe pediatric respiratory disease.     

Allergens, viruses, and asthma exacerbations

In adults and children with asthma, viral infections (rhinovirus [RV] infection being the most prevalent) will often trigger an increase in symptomatology. The mechanisms responsible for viral-induced exacerbations remain uncertain. Proposed mechanisms include direct infection of the lower respiratory tract, the inflammatory response to viruses, increases in bronchial responsiveness and up-regulation of intercellular adhesion molecule-1 expression in bronchial epithelium. In addition, exposure to allergens, especially seasonal allergens, in sensitized asthmatic individuals have been implicated in asthma attacks. Increased levels of exposure in sensitized asthmatics have been related to increases in hospital admissions and emergency room visits, increased bronchial hyperresponsiveness, increased levels of exhaled nitric oxide, lower levels of lung function, increased treatment requirements, and even increased mortality. In recent years studies have suggested that viruses and allergens may have a synergistic effect on individuals with asthma, thus having a greater influence on exacerbation rate together than either factor alone. Models of experimentally induced RV infection in both allergic and nonallergic individuals using bronchoalveolar lavage and segmental allergen challenge have helped researchers to investigate the possibility of an interaction between allergen sensitization, exposure, and virus infection and their role in the induction of an asthma exacerbation. This review aims to summarize the evidence supporting the role of viruses (in particular RV) as well as the role of, and interaction with, allergen sensitization and exposure on exacerbations of asthma.     

支气管哮喘儿童急性发作期诱导痰液T细胞亚群及自然杀伤T细胞的变化

目的 分析支气管哮喘(简称哮喘)儿童急性发作期及缓解期诱导痰液T细胞亚群及自然杀伤T细胞(NKT细胞)的变化,探讨T细胞及NKT细胞在儿童哮喘气道炎症中的作用.方法 选取18例哮喘急性发作、21例哮喘缓解期及12名正常儿童的痰液,采用流式细胞术比较各组儿童诱导痰液CD3、CD4、CD8、NKT(CD3~+ CD56~+)百分比及CD4/CD8比值.结果 哮喘急性发作组CD4细胞百分比[(43.75±13.5)%]明显高于缓解期组[(37.04±7.11)%]和正常对照组[(33.57±7.54)%](P＜0.05),CD8细胞百分比[(21.10±6.10)%]明显低于缓解期组[(28.67±5.32)%]和正常对照组[(28.31±9.46)%](P<0.05),CD4/CD8比值(2.14±0.94)高于缓解期组(1.33±0.35)和正常对照组(1.31±0.42)(P＜0.05),CD4、CD8细胞百分比及CD4/CD8缓解期组和正常对照组差异无统计学意义(P>0.05),急性发作组CD4/CD8比值与嗜酸粒细胞百分比呈正相关(r=0.559,P＜0.05).缓解期组CD4/CD8比值与嗜酸粒细胞无相关性(r=0.398,P>0.05).急性发作组CD3+ CD56+细胞百分比[(3.33±1.69)%]略高于缓解组[(3.09±1.23)%]及对照组[(2.94±0.87)%],但差异无统计学意义(P>0.05).CD3- CD56+细胞百分比在三组之间无统计学差异(P>0.05).结论 儿童哮喘急性发作期,气道内CD4细胞占优势,CD4/CD8细胞比例失衡,CD4细胞可能介导儿童哮喘气道炎症过程.     

支气管哮喘气道炎症和哮喘控制与肺炎支原体感染的相关性研究

目的 探讨支气管哮喘(简称哮喘)患者的气道炎症、哮喘控制与肺炎支原体(MP)感染的关系。方法 选择2010年6月至2012年10月浙江大学医学院附属第二医院收治的支气管哮喘急性发作期患者114例和缓解期患者116例，检测两组MP特异IgM和IgG，比较其感染率；比较两组中有、无MP感染患者间痰嗜酸粒细胞(EOS)计数、血清总免疫球蛋白E(IgE)、第一秒用力呼气容积占预计值百分比(FEV1% pred)及哮喘控制测试(ACT)评分；并行相关性分析。结果 急性发作患者MP感染率(41.2%)明显高于缓解期患者(22.4%，P<0.05)；MP感染患者痰EOS计数、血清总IgE均高于无MP感染患者，而FEV1%pred及ACT评分均低于无MP感染患者，两者差异有统计学意义(P<0.05)；两组感染率与各组感染阳性患者的FEV1%pred、ACT评分呈负相关(r=-0.356、-0.456)，与各组MP感染阳性患者的血清总IgE及痰EOS计数呈正相关(r=0.756、0.356)。结论 无论哮喘急性发作期还是缓解期，MP感染都是不可忽视的因素，且相较于慢性缓解期，更多见于哮喘急性发作期。     

Pneumoperitoneum recurring concomitantly with asthmatic exacerbation

We report a patient with pneumoperitoneum that recurred concomitantly with asthmatic exacerbation. The patient was a 71-year-old man with a medical history of bronchial asthma. Chest X-rays obtained during asthmatic exacerbation showed intra-abdominal air beneath his diaphragm. Subsequently, a computed tomography scan of his chest confirmed mediastinal emphysema and intra-abdominal air beneath his diaphragm. The intra-abdominal air disappeared after his asthmatic exacerbation was relieved by treatment. The patient showed recurrent pneumoperitoneum concomitant with asthmatic exacerbation. The cause of his pneumoperitoneum was conjectured to be the movement of air from the mediastinum to the peritoneal cavity through the sternocostal triangle.     

Viral infection in asthma

In bronchial asthma, respiratory virus infection involves several issues: 1) respiratory virus infection in infancy is a risk factor for, and may predispose to, the development of asthma later in life; 2) respiratory virus infection is associated with the acute exacerbation of bronchial asthma; and, 3) glucocorticosteroids (GC) are not adequate for controlling asthma-related symptoms upon respiratory virus infection. Various cells, inflammatory mediators and cytokines participate in the production of airway inflammation upon respiratory virus infection. Bronchial epithelial cells are a site of infection and replication of respiratory virus. They actively participate in the production of airway inflammation: 1) they produce various proinflammatory cytokines, chemokines and mediators; and, 2) they undergo apoptosis, thereby impairing the repair process. It is therefore important to understand the role of bronchial epithelial cells in the pathophysiology of bronchial asthma. In this review, the interaction between viral infection and asthma is discussed to elucidate the role of bronchial epithelial cells in viral infection.     

苏州地区儿童急性呼吸道感染鼻咽部病毒病原学分析

目的 分析苏州地区儿童急性呼吸道感染（ARTI）鼻咽部病毒病原学的特征,探讨其临床意义.方法 选择2010年11月-2012年2月于苏州市立医院本部儿科病房住院治疗的ARTI患儿367例,分别按性别、年龄及季节进行分组,采用直接荧光免疫法对患儿鼻咽部采样物进行呼吸道合胞病毒（RSV）、腺病毒（Adv）、流感病毒A（Flu A）、流感病毒B（Flu B）、副流感病毒1（PIV Ⅰ）、副流感病毒2（PIV Ⅱ）、副流感病毒3（PIV Ⅲ）检测.结果 367例ARTI患儿中检测出阳性结果有148例（40.33%）,按阳性率从高到低依次为RSV 112例（30.52%）、PIV Ⅲ 28例（7.63%）、Adv 10例（2.72%）、Flu A 4例（1.09%）、Flu B 3例（0.82%）.≤11个月患儿病毒阳性率和RSV阳性率均高于其他两个年龄段（P＜0.05）;冬季病毒阳性率和RSV阳性率均高于其他3个季节（P＜0.05）.结论 病毒感染是ARTI的主要病因之一,RSV和PIV Ⅲ是苏州地区儿童病毒感染的主要病原体,且婴幼儿和冬季病毒感染更为明显.     

Q fever in acute exacerbation of chronic lower respiratory tract infection]

We studied the effect of Q fever in acute exacerbation of chronic lower respiratory tract infection. The subjects consisted of 80 cases with acute exacerbation of chronic lower respiratory tract infection treated during the period from March 2002 till October 2004. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit. Two cases (2.5%) were positive for IgM in the acute stage, and were diagnosed as having acute infection by C. burnetii. They were elderly women with bronchiectasis, aged 76 and 82. They had no history of keeping cats or dogs, but the onset of acute exacerbation of chronic lower respiratory tract infection was June and March which is the breeding seasons for cats and dogs. Acute exacerbation of chronic lower respiratory tract infection were considerd to be a mixed infection with Pseudomonas aeruginosa (the 76-year-case) and Haemophilus influenzae (the 82-year-case). It is concluded that C. burnetii can induce exacerbation of chronic lower respiratory tract infection, their cases were considerd to be mixed infection with C. burnetii and other bacteria.     

Persistence of rhinovirus RNA and IP-10 gene expression after acute asthma

Background and objective: Viral nucleic acid may be detected for up to 6 months after an acute asthma deterioration, but the pattern and consequences of viral persistence after acute asthma are incompletely understood. This study investigates the frequency of viral persistence after acute asthma, assesses viral infectivity and determines the host inflammatory responses to viral persistence. Methods: Adults and children presenting to hospital with acute asthma and a confirmed respiratory virus infection were studied acutely and at recovery 4–6 weeks later by clinical evaluation and induced sputum for viral and inflammatory mediator detection. Results: Viral RNA was detected during both acute asthma and recovery visits in 17 subjects (viral persistence), whereas in 22 subjects viral RNA had cleared by recovery (viral clearance). The following viruses were detected at recovery: human rhinovirus: 16; respiratory syncytial virus: 2; influenza: 2. In subjects with viral persistence, eight isolates were different to the virus detected at Visit 1. Forty‐four per cent of the human rhinovirus isolates were infective at recovery. Asthma and infection severity were similar in the viral clearance and viral persistence groups. Viral persistence was associated with elevated IL‐10 mRNA and inducible protein‐10 gene expression. Conclusions: Respiratory viral detection after acute asthma is common, and most often persistence is with non‐infective human rhinovirus. There is a host inflammatory response with an altered cytokine environment, and the viral RNA can be source of persistent infection. These effects may have longer‐term consequences in asthma.     

呼吸道病毒感染诱导哮喘急性发作的临床分析

目的观察临床缓解期哮喘患者并发上呼吸道病毒感染(简称上感)后哮喘发作的比例及特点。提出“呼吸道病毒感染诱导哮喘发作窗”的新概念。方法哮喘患者并发上感后1天内即来我院诊治,于2003年8月~2004年8月对上述来诊患者110例进行临床观察。当天均行血常规,胸片,肺功能及取鼻咽分泌物以碱性磷酸酶桥联酶标法(APAAP)检测病毒抗原等检查。每例观察7天,记录上感及哮喘症状。结果110例并发上感68例有哮喘发作,第1天哮喘发作4例,第2天为6例,第3天为27例,第4天为29例,第5天为2例,第6天和第7天均为0例。哮喘发作程度:轻度为24例,中度为36例,重度为8例。哮喘发作患者病毒检测阳性为59例,鼻病毒为23例,流感病毒A和B为18例。结论临床缓解期患者并发上感后哮喘发作的比例为61.8%,3天后发作比例约为85.3%。病毒感染诱导哮喘发作窗初步设定在3天,在此窗内及时给予干预措施可能避免大部分哮喘患者发作。