Bronchitis: Causes and Treatment

In: Handbook of Pulmonary Diseases: Etiology... Editor: Krisztián Fodor and Antal Tóth ISBN: 978-1-60741-898-6 © 2009 Nova Science Publishers, Inc. ...
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In: Handbook of Pulmonary Diseases: Etiology... Editor: Krisztián Fodor and Antal Tóth

ISBN: 978-1-60741-898-6 © 2009 Nova Science Publishers, Inc.

Chapter 3

Bronchitis: Causes and Treatment Tapan K. Mukherjee* Indian Institute of Science Education and Research, MGSIPA Complex, Sector -26, Chandigarh-160019, India.

Abstract Bronchitis is the inflammation of the bronchi (bronchial tubes) that carry air to the lungs. The inflammatory reactions may be caused by virus (e.g. Respiratory Syncytial Virus, Parainfluenza and Influenza Virus, Adenovirus, Measles Virus), as well as allergens, airborne particles, smoking and environmental pollutants. Secondary infections by typical and atypical bacteria and mycoplasma may complicate bronchitis. The inflammatory reactions are characterized by an increase in inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-18 and TNFα, which might be responsible for the infiltration of neutrophils, macrophages, CD8+ T cells into the airway walls of the small bronchial tubes. Inflammation of the bronchial glands leads to their hypertrophy and hypersecretion of mucus. Bronchitis can be acute and short lived or chronic which lasts for a long time and is often recurring in nature. In symptomatic bronchitis, the common symptoms are coughing, wheezing, breathlessness, chest congestion, mucus secretion, soar throat, chills and fever. In asymptomatic bronchitis not all of the above mentioned symptoms are noticed in all patients. Cessation of smoking, keeping away from environmental pollutants, antibiotic treatment (in case of a secondary infection) and respiratory exercise may improve bronchitic conditions. Controversy remains regarding the usefulness of therapeutic agents like corticosteroids, β-agonists and anticholinergic for the treatment of bronchitis. Antiviral and immunoglobulin agents were also used by several investigators but with little success. A better understanding of the cellular and molecular mechanism of bronchitis can help to promote new drug development.

*

Corresponding author: E-mail: [email protected]

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The Bronchitis Bronchitis is an inflammation of the bronchi, the large airway inside the lung (Gwaltney JM, 2005). Bronchitis is different from bronchiolitis, which is an inflammation of the small airways that lack mucus secreting glands and cartilage, and also from bronchiectasis, which is the permanent dilation and destruction of bronchi involving chronic cough (Breslow L, 2002). Sometimes the definition of bronchitis is extended to include inflammation of air passages between the nose and lungs, including the trachea (windpipe) and the bronchi (Longe JL, 2006; Krapp K, 2005). Similarly, trachiobronchitis refers to the inflammation of the trachea and bronchi (Breslow L, 2002) causing bronchial glands (Goblet cells) of the airway passages or bronchial tubes to increase the production of mucus with a resultant thick and yellow or gray colored mucus being coughed up. Bronchitis may be either acute or chronic.

Acute Bronchitis Acute bronchitis begins as a respiratory tract infection that manifest as the common cold. Usually, winter and early spring is the peak time for occurrences (Kuzel RJ, 1993). It occurs most commonly in children younger than 2 years. However, children aged 9-15 years are also highly susceptible. Therefore, bronchitis is one of the top 5 reasons for childhood physician visits in most countries. Acute bronchitis affects approximately only 5% of adults annually (Macfarlane J, 2001; Benson V, 1998). In the United States of America, acute bronchitis is the ninth most common illness among outpatients (DeLozier JE, 1991). Patients typically suffer from rhinorrhea, cough, low grade fever, tachypnea, chest wall retractions, nasal flaring, cyanosis, expiratory wheezing, hypoxemia, sore throat, back and muscle pain (Horst PS, 1994). In neonates, apnea may be the only sign of the disease (Orga PL, 2004). Cough in these children is usually accompanied by an initial watery nasal discharge. After several days, the nasal discharge becomes thicker and colored or opaque. It then becomes clear again and has a mucoid watery consistency before it spontaneously resolves within 7-10 days. Purulent nasal discharge is common with viral respiratory pathogens and by itself, does not imply a bacterial etiology to the infection. Initially, the cough is dry and may sound harsh or raspy which subsequently loosens and becomes productive. Children younger than 5 years rarely expectorate. In this age group, sputum is usually seen in vomitus (ie. posttussive emesis). Patients frequently note a rattling sound in the chest. Hemoptysis, a burning discomfort in the chest and dyspnea may be present. If there is no serious secondary bacterial infections the patient recovers within days.

Chronic Bronchitis Chronic bronchitis affects people of all ages but is more prevalent in people over 45 years of age. As opposed to acute bronchitis chronic bronchitis results from inhalation of respiratory tract irritants, the most common being cigarette smoke, air pollution, chemical fumes, fungal spores, dust, and other environmental irritants. Chronic bronchitis develops slowly over time

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with the irritants paralyzing or snapping off the cilia of the cells that line the respiratory tract and normally move the mucus along. The airway become clogged, inflamed and narrowed and this leads to difficulty in breathing (Longe JL, 2006). There are two types of chronic bronchitis due to cigarette smoking. 1. Simple chronic bronchitis and 2. chronic obstructive bronchitis. Patients with simple chronic bronchitis lack airflow obstruction on pulmonary function test or spirometry, while those with chronic obstructive bronchitis exhibit reduced airflow rates. Some patients with simple chronic bronchitis progress to the chronic obstructive form of bronchitis and most of these also have emphysema (Breslow L, 2002). Brunton S (2004) noted that adult patients with chronic bronchitis have a history of persistent cough that produces yellow, white or greenish sputum on most days for at least 3 months of the year for more than 2 consecutive years. Wheezing and reports of breathlessness are also common. Pulmonary function testing in these adult patients reveals irreversible reduction in maximum airflow velocity. Repeated irritation of the bronchial tubes by continued exposure to environmental pollutants and cigarette smoke are the major causes for chronic bronchitis.

Epidemiology of Bronchitis Hospital admission rates in USA and Europe for bronchiolitis have reported to be around 30 per 1000 for children younger than 1 year (Dayan PS, 2004; Simoes EA, 2003). High-risk groups for severe infections are infants younger than 6 weeks; premature infants and those with chronic lung disease of prematurity, congenital heart disease, neurological disease (Purcell K, 2004) or immunodeficiency (Hall CB, 1986). The mechanisms that contribute to increased disease severity in infants in each of these risk groups is not fully understood, but are probably related to abnormalities in physiological and immunological responses to infection. Bronchiolitis associated deaths are fortunately very rare. Rates in USA in late 1990s were reported to be 2.0 per 100000 live births (Holman RC, 2003). This rate has remained stable in the USA since 1979, whereas in the UK, the post-neonatal mortality rate due to bronchiolitis fell from 21.47 per 100000 in 1979 to 1.82 per 100000 in 2000. Risk factors for death are low birth weight, increased birth order, young maternal age, unmarried mother and tobacco use during pregnancy (Holman RC, 2003). However, an epidemiological study in the UK (Fleming DM, 2005) which compared excess in deaths during (Respiratory Syncytial Virus) RSV inactive weeks, suggested that RSV could have had a greater influence on mortality than that estimated by direct ascertainment of respiratory certified deaths. For babies aged 1-12 months, the RSV-attributed winter mortality rate per 100000, averaged over 11 winters, was 2.9 for respiratory causes, compared with 8.4 for all causes (Fleming DM, 2005). In USA, Hispanic children are more likely to be admitted as emergency cases than the general population (Mansbach JM, 2005). Native American and Alaskan infants likewise have slightly higher rates of hospital admission than the general populations and this shows strikingly regional variation, which is specially high in Alaska and the southwest (70.9 and 48.2 per 1000 infants respectively, compared with 27.4 hospital admission per 1000 infants in the general population of the USA (Holman RC, 2004). Inuit infants living in Baffin Island, Nunavut, have the highest prevalence of bronchiolitis, requiring hospital admissions, in the world (197 per 1000 infants) (Creery D, 2005). These findings are probably due to a

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combination of socioeconomic factors and reduced access to health care in remote areas. Findings could also be biased because children were more severely ill by the time they arrived at hospital emergency departments and therefore were more likely to be admitted than sent back home over long distances or difficult terrain.

Examination and Tests for Bronchitis Examination of patients lungs with a stethoscope can be used as a preliminary examination schedule. Abnormal sounds in the lungs called rales or other abnormal breathing sounds may be heard. Tests may include: a chest X-ray (to rule out a condition like pneumonia), and sometimes a breathing test (called spirometry) to rule out asthma. Pulse oximetry helps determine the amount of oxygen in blood. This quick and painless test uses a device that is placed onto the end of a finger. Arterial blood gas is a more exact measure of oxygen and carbon dioxide levels, but the inherent testing procedure is painful. Alternatively, sputum samples can be taken to check for signs of bacterial infection.

Asthma and Bronchitis Defining chronic bronchitis and its prevalence in childhood has been complicated by the significant clinical overlap with asthma. Recurrent episodes of acute or chronic bronchitis are unusual and should alert the health care provider of the likelihood of asthma. In particular, bronchitis is often diagnosed repeatedly in children in whom asthma has remained undiagnosed for many years. Additionally, the hereditary factors might also help in the early diagnosis of the disease. For eg, multiple episodes of bronchitis might suggest previously undiagnosed asthma in a parent or sibling. The diagnosis of asthmatic bronchitis might be simply asthma. Chronic bronchitis has been defined as a complex of symptoms including cough that lasts for more than a month or recurrent productive cough that may be associated with wheezing or crackles on ausculation. Interestingly, these are also the working definitions of asthma.

Chronic Asthmatic Bronchitis Chronic asthmatic bronchitis refers to an underlying asthmatic problem in patients in whom asthma has become so persistent that clinically significant chronic airflow obstruction is present despite anti-asthmatic therapy. The symptoms of chronic bronchitis are also present, but patients tend to have increased severity and frequency. Bronchial asthma is not classified as bronchitis. Asthma, chronic bronchitis and emphysema all diffusively affect the bronchial tree and may give rise to the syndrome of wheezing, coughing, and shortness of breath. It is clinically difficult to distinguish these disorders and for this reason, estimates of their prevalence are not entirely accurate. It should be understood that 50% of children with asthma develop their initial symptoms before their first birthday. Many young children who suffer from undiagnosed respiratory infections such as wheezy bronchitis, asthmatic bronchitis or bronchitis are

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misdiagnosed as suffering from asthma despite ample evidence that there is a variable airflow limitation. Another cause of under diagnosis is the failure to recognize that asthma may accompany other chronic respiratory diseases, such as bronchopulmonary dysplasia, cystic fibrosis, or recurrent group which can dominate the clinical picture.

Chronic Obstructive Pulmonary Disease and Bronchitis Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are two different diseases. Chronic bronchitis with air-flow obstruction is called as COPD. Physicians often classify chronic bronchitis under the term COPD or chronic obstructive airway disease (COAD), that describes not only bronchial damage but also other lung disorders often affiliated with environmental factors such as emphysema and asbestosis. This complex disease state consists of emphysema (centrilobular and panacinar), small airway disease and chronic bronchitis with air flow obstruction (Szilasi M, 2006). Chronic bronchitis without airflow obstruction may not result in emphysema. The role of chronic mucus hypersecretion in the development of chronic airflow obstruction is still controversial. Although the two conditions may coexist in the same subject, several reports have suggested that chronic bronchitis and chronic airflow obstruction should be considered separate diseases rather than manifestations of a single disease (Anthonisen NR, 1986; Traver G, 1979). However, another study in a large random population (Vestbo J, 1996) showed that chronic mucus hypersecretion was significantly associated with both an excessive decline of Forced Expiatory Volume (FEV1) and an increased risk of subsequent hospitalization due to COPD thereby supporting the concept of a causal role of chronic mucus hypersecretion in the development of chronic airflow obstruction. In the study of Vestbo 1996, the chronic bronchitic subjects were selected for both chronic mucus hypersecretion and chronic airflow obstruction, and therefore represented a subset of all chronic bronchitic individuals. Whether bronchial-gland inflammation is also a characteristic feature of chronic bronchitis without airflow obstruction remains to be investigated. Smoking is the most significant risk factor for patients with chronic bronchitis plus airflow obstruction/COPD, although an important (though small) subset of chronic bronchitis and COPD patients are nonsmokers. However, given the fact that only 15-20% of smokers develop chronic bronchitis or COPD largely indicates that apart from smoking, a genetic component might also be an operating factor for COPD (Mannino DM, 2002; Barnes PJ, 2002). In addition, patients with COPD/chronic bronchitis often do not respond to corticosteroid therapy, whereas patients with chronic bronchitis alone do (Barnes PJ, 2002). Very recently, an article by Szilasi, 2006 discussed in detail the differences of chronic bronchitis alone and COPD.

Factors Affecting Acute Bronchitis Acute bronchitis is generally caused by respiratory infections of which approximately 90% are viral in origin and 10% bacterial. This is why acute bronchitis is said to be infectious. The

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most common cause of acute and chronic bronchitis in the pediatric population is: viral infections (Adenovirus, Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus, Rhinovirus, Coxsackie Virus, Herpes Simplex Virus) (Smyth R, 2006). A recent French study involving adults who had been vaccinated against influenza showed a viral cause in 37% of 164 cases of acute bronchitis, of which 21% were caused by rhinovirus (Freymuth F, 2004). Thus, the isolation and yield of specific pathogens varies according to several factors, including the presence or absence of an epidemic, the seasons and the influenza vaccination status of the population. Secondary bacterial infections are also part of an acute respiratory infection (extremely rare in nonsmokers without cystic fibrosis). The most common bacterial pathogen that causes lower respiratory tract infections in children of all age groups is Streptococcus pneumonia. Moraxella catarrhalis, Haemophilus influenza (nontypeable) and Clamydia pneumonia (Taiwan acute respiratory agent) are significant pathogens in preschool children below age 5. Mycoplasma pneumonia may be significant in school children aged 5-8 years. Bacterial species commonly implicated in community acquired pneumonias were isolated from the sputum in a minority of patients with acute bronchitis (MacFarlane J, 2001). However, the role of these species in the disease or its attendant symptoms remains unclear, since bronchial biopsies have not shown bacterial invasion. In some cases, atypical bacteria are important causes, including Bordetella Pertussis, Chlamydophila (Chlamydia) pneumonia, and Mycoplasma pneumonia (MacFarlane J, 2001). Some data have suggested that B. pertussis may underlie 13-32% of cases of cough lasting six days or longer, although in a recent perspective study, B. pertussis comprised of only 1% of the cases of acute bronchitis (Ward JI, 2005). Children with tracheostomies are often colonized with an array of flora, including α and γHemolytic streptococci. With acute exacerbations of tracheobronchitis in these patients, pathogenic flora may include Pseudomonas aeruginosa and Staphylococcus aureus (including methicillin resistant strains), among other pathogens. Children predisposed to orthopharyngeal aspiration, particularly those with compromised protective airway mechanisms, may become infected with oral anaerobic strains of streptococci. Air pollutants, bronchial tube irritants and second-hand smoke, allergies, chronic aspiration or gastroesophageal reflux and fungal infections may also cause acute bronchitis.

Factors Affecting Chronic Bronchitis A chronic or recurrent insult to the airway epithelium, such as recurrent aspiration or repeated viral infection may contribute to chronic bronchitis in childhood. Thus, it may be caused by repeated attacks of acute bronchitis, which can weaken and irritate bronchial airways with time. Following damage to the airway lining, chronic infection by commonly isolated airway organisms may occur. Industrial pollution is a common cause; however, the chief reason is heavy long term exposure to cigarette smoke. In children, chronic bronchitis follows either an endogenous response (eg. excessive inflammation) to acute air flow injury or continuous exposure to certain obnoxious environmental agents (eg. allergens or irritants). The incidence of bronchiolitis and

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bronchitis in children under the age of 5 is correlated to passive smoking (DiFranza JR, 1996). An airway that undergoes such an insult responds quickly with bronchospasm and cough, followed by inflammation, edema, and mucus production. The role of irritant exposure, particularly cigarette smoke and airborne particulates, in recurrent (wheezy) bronchitis and asthma is becoming clear. Kreindler JL (2005) demonstrated that the ion transport phenotype of normal human bronchial epithelial cells exposed to cigarette smoke is similar to that of cystic fibrosis epithelia, in which sodium is absorbed in a ratio out of proportion with chloride secretion in the setting of increased mucus production. These findings suggest that the negative effects of cigarette smoke on mucociliary clearance may be mediated through alteration in ion transport. McConnell R (2003) noted that organic carbon and nitrogen dioxide airborne particulates were associated with chronic symptoms of bronchitis among children with asthma in Southern California. Recurrent episodes of acute or chronic bronchitis may be associate with immunodeficiency. Ozkan H (2005) studied immunoglobin A (IgA) and immunoglobin G (IgG) deficiency in children who had recurrent sinopulmonary infection. The overall frequency of antibody defects was found to be 19.1%. IgA deficiency was observed in 9.3% cases. IgG subclass deficiency was observed in 8.4% cases and both IgA and IgG subclass deficiencies were observed in 1.4% cases. The prevalence of IgA and IgG subclass deficiencies was 25% in patients with recurrent upper respiratory tract infections and 22% in patients with recurrent pulmonary infections and 12.3% in patients with recurrent bronchiolitis.

Pathophysiology of Acute Bronchitis Acute bronchitis was originally described in the 1800s as an inflammatory response to infections of the epithelium of the bronchi. In clinical terms acute bronchitis implies a self limited inflammation of the large airways of the lung that is characterized by cough without pneumonia. Over the years, this inflammation has been shown to be the result of a sometimes complex and varied chain of events. The inflammatory response leads to bronchial epithelial injury, which causes airway hyper responsiveness and mucus production (Treanor JJ, 2000). Epithelial cells desquamation and denuding of the airway epithelium to basement membrane in association with the presence of a lymphocytic cellular infiltrate have been demonstrated after influenza virus mediated tracheobronchitis (Walsh JJ, 1961). Microscopic examination has shown thickening of the bronchial and tracheal mucosa corresponding to the inflamed areas. Such pathological findings are consistent with reports of proximal lower airway inflammation confined to the bronchi, as detected by Positron Emission Tomography (PET) with 18Ffluorodeoxyglucose as a tracer, in the setting of acute bronchitis (Kicska G, 2003). If the patient is in otherwise good health, the mucous membrane returns to normal, heralding recovery from the initial active infection, which usually lasts for several days. However, there are wide variations in the anatomical distribution of many pathogens that cause acute bronchitis. In a study involving volunteers exposed to rhinovirus infections, virus was detected in specimens of induced sputum obtained from all subjects in approximately one third of the bronchial brushing specimens (Mosser AG, 2005). Such data indicating viral infection of the lower airways may help to explain the relationship observed between

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rhinovirus infection (and other presumed upper respiratory viral infections) and exacerbation of asthma. Thus, although its name suggests only large-air way disease, acute bronchitis may be accompanied by an array of symptoms, depending on the degree of viral involvement of the large and small airways.

Pathophysiology of Chronic Bronchitis Chronic bronchitis is a recurring inflammation and degeneration of the bronchial tubes that may be associated with active infection. Chronic bronchitis is often a part of an underlying disease process, such as asthma, cystic fibrosis, dyskinetic cilia syndrome, foreign body aspiration or exposure to an airway irritant. Recurrent tracheobronchitis may also be seen in patients with tracheostomy or with certain forms of immunodeficiency. In all these patient groups, chronic bronchitis should not be the primary diagnosis because it does not describe the pathology of the underlying disorder. Patients with chronic bronchitis have more mucus than normal because of either increased production or decreased clearance. Coughing is the mechanism by which excess secretion is cleared. In adults, chronic bronchitis results from hyper secretion of mucus in the bronchi due to hypertrophy of the submucosal mucus producing glands and increased number of goblet cells within the epithelium. In most patients, this results from exposure to cigarette smoke. Mucociliary clearance is delayed because of excessive mucus production and loss of ciliated cells leading to productive cough.

Inflammatory Cells in Bronchitis During bronchitis increased level of inflammatory reactions is noticed in the bronchial tubes. In a number of recent studies, the data suggested that neutrophil but not eosinophil mediated inflammatory reactions are part of bronchial pathophysiology. For example it was assessed whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 weeks) with acute bronchiolitis. The outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 and albumin levels significantly rose with respiratory rate. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggested that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis (Marguest C, 2008). A number of studies checked the infiltration of inflammatory cells in various cellular compartments in bronchial tubes. These studies of bronchial biopsy specimens from subjects with chronic bronchitis have provided evidence for an inflammatory process, consisting

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predominantly of mononuclear cells in the large airways of these subjects (Fournier M, 1989). These studies, however, have examined only the epithelial (Fournier M, 1989; Saetta M, 1993) or submucosal (Ollerenshaw SL, 1992; Saetta M, 1993) compartments, whereas little information is available on the inflammatory process in these subject's bronchial glands. Similarly other studies also showed the inflammatory changes in the large airways of subjects with chronic bronchitis. There was a predominance of mononuclear cells in the airway wall (Di Stefano, AG, 1996) and of neutrophils in the airway lumen (Thompson AB, 1989; Martin TR, 1985; Linden M, 1993). Among all the studies performed on bronchial biopsies, only one (Pesci A, 1994) was able to investigate the bronchial-gland compartment and demonstrated a mast-cell infiltration in subjects with chronic bronchitis. In a comparatively recent study it has been shown that smokers with symptoms of chronic bronchitis have an increased number of inflammatory cells in their bronchial glands when compared with asymptomatic smokers. This inflammatory process consists predominantly of neutrophils and macrophages, and of an increased proportion of CD8+ T-lymphocytes. This study showed an increased number of neutrophils in the bronchial glands of subjects with chronic bronchitis, providing evidence for neutrophilia not only in the airway lumen but also in the airway wall of these subjects. This has contributed to a better understanding of the apparent discrepancy between luminal and parenchymal findings in this disease. Inflammatory cells are increased in bronchial submucosal glands and mucosa of large airways in smokers with chronic bronchitis. Gland-associated plasma cells express IL-4 and these likely promote mucus hypersecretion. Histologically, airway inflammation, hypertrophy of submucosal mucus-secreting glands and goblet cell hyperplasia are abnormalities found in the airways of smokers with chronic bronchitis (Reid L 1985; Mulllen J BM, 1987). Although an increase in gland size (i.e., hypertrophy) is a factor contributing to increased airway mucus production (Reid L, 1985), airway inflammation (including the presence of lymphocytes and plasma cells) rather than gland size per se is the feature most closely associated with expectoration of sputum (Mullen J BM.1987; Saetta M, 1997). Hypersecretion from mucus-secreting glands may arise subsequently to chronic inflammation via the release of selected proinflammatory cytokines that include IL-4, a multifunctional cytokine that can facilitate the differentiation of both mucus-secreting tissue and B lymphocytes (Temann U-A, 1997; Dabbagh K, 1999). The numbers of CD45+ inflammatory cells, plasma cells, and mast cells are greater in the large airway walls of smokers with chronic bronchitis than in (asymptomatic) AS or smokers with chronic bronchitis +AO. The frequent presence of IL-4 expressing plasma cells associated with the increased mucin present in the bronchial submucosal glands of smokers with chronic bronchitis supports the modulator effect of plasma cells and associated IL-4 on hypersecretion of mucus in chronic bronchitis (Jonsson JS, 1998). Besides IL-4 some other proinflammatory cytokines also take a contributory role in the complication of bronchitis. Previous findings suggest a possible recruitment of various inflammatory cells by epithelium-derived factors such as IL-8 (Standiford, TJ, 1990), a potent neutrophil chemoattractant, which has been found to be increased in the sputum (Keatings VM, 1996) and bronchial washings of subjects with chronic bronchitis (Riise GC, 1995). Bont and colleagues noted depressed peripheral lymphocyte function associated with raised plasma IL-8 concentrations in children with severe bronchiolitis. CXCL8 is a CXC-chemokine that promotes neutrophil chemotaxis and survival and neutrophil are the predominant cell type present in the bronchial secretions of children with severe bronchiolitis (McNamara PS, 2003).

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Studies in Liverpool, UK have shown that the amount of CXC chemokine mRNA in the nasal aspirants of infants with bronchiolitis correlates with the severity of disease (Smyth RL, 2002). The lower airways of infants with severe RSV bronchiolitis likewise contained large quantities of CXC-chemokines, which included CXCL8 and CXCL10 (Tekkanat KK, 2002). One very recent study analyzed polymorphism of IL-10 -1802 G/A, IL-18 -137 G/C, TLR + 896 A/G and IFNγ + 874 T/A in 139 infants under 6 months of age hospitalized with bronchiolitis and 400 unselected blood donors. Causative viruses were determined by PCR. Infants with bronchiolitis associated with a virus other than RSV (N=18), were more than IL10 -1082 allele G non-carriers [i.c., homozygous for allele A (AA)] than controls (66.7% vs 28.0%, P

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