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Lung Infections C 4 Pathogenesis of Lower Respiratory Tract

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Lung Infections C 4 Pathogenesis of Lower Respiratory Tract 302 Thorax 1998;53:302–307 Lung infections c 4 Series editor: S L Hill Thorax: first published as 10.1136/thx.53.4.302 on 1 April 1998. Downloaded from Pathogenesis of lower respiratory tract infections due to Chlamydia, Mycoplasma, Legionella and viruses Paul Andersen Acute infection of the lower respiratory tract terminal organelle.18 Metabolic and ultrastruc- comprises bronchitis, bronchiolitis, and pneu- tural alterations in the aVected cell are seen and monia. From a clinical point of view it may be these result in epithelial cell damage and cilio- diYcult to distinguish these disease entities stasis. Some epithelial cell lines produce and one infection may progress into another. cytokines when stimulated with other bacteria The most common pathogens causing these such as Escherichia coli,21 and epithelial cells infections are the primary respiratory viruses might therefore play a more active role in the (respiratory syncytial virus (RSV), influenza mucosal immune response after extracellular virus, adenoviruses, parainfluenza virus, and bacterial infection. In acute respiratory viral rhinovirus12), Mycoplasma pneumoniae,3 and diseases a number of diVerent inflammatory Chlamydia species.4–6 Legionella may cause mediators such as kinins and cytokines have pneumonia and non-pneumonic upper respira- also been demonstrated. In some infections tory tract infection and approximately 85% of c such as influenza extensive infiltrations with ases are caused by L pneumophila. Long lasting polymorphonuclear leucocytes (PMN), sequelae such as bronchiectasis, lung fibrosis, oedema, and degeneration of epithelial cells are and decreased lung function are seen after seen,22 whereas in others such as rhinovirus 7–10 lower respiratory tract infections and it has infection the cytopathic eVects are either http://thorax.bmj.com/ been debated whether respiratory tract infec- absent or minor in degree.23 tion can cause chronic bronchial asthma.6 11–13 BRONCHITIS AND BRONCHIAL HYPERREACTIVITY Acute bronchitis and bronchiolitis The cardinal symptom of acute bronchitis is Acute bronchitis is an inflammatory condition cough, while wheezing occurs in 10–90% of of the bronchi often caused by infectious cases.614152425 Transient bronchial hyperreac- agents, although in many cases no aetiology tivity has been found several weeks after influ- can be established.14 15 It shares many patho- enza A infection in subjects with no previous logical and clinical features with bronchiolitis, history of bronchospasm,25 and in 40 patients on September 27, 2021 by guest. Protected copyright. and the same agents may induce both condi- with acute bronchitis and without pre-existing tions. Most cases of acute bronchitis of known pulmonary disease wheezing was reported in aetiology are due to respiratory viruses such as 62%.14 A reduction in forced expiratory volume influenza virus, adenovirus, RSV, rhinovirus, in one second (FEV1) and peak expiratory flow and coronavirus,1216 and a few are caused by (PEF) was found during the acute illness, and M pneumoniae, Bordetella pertussis and C 37% had bronchial hyperreactivity measured pneumoniae.451517 Legionella infections limited by histamine challenge testing six weeks later.14 to the bronchial tree are not described. In patients with bronchial asthma26 27 it has been shown that acute exacerbations of wheez- ADHERENCE OF PATHOGENS ing and decreased PEF were associated with The pathogenesis has not been studied for all respiratory tract infections caused by rhinovi- agents, but the transmission of disease is ruses, coronaviruses, influenza virus, RSV, thought to occur through droplet spread from parainfluenza virus, and Chlamydia in 80–85% an infected person. After inhalation the infec- of cases. Thus, in both asthmatic and non- tious agent may adhere to diVerent receptors asthmatic patients pulmonary symptoms and such as acid containing glycoproteins or the changes in airway function occur during and adhesion molecule ICAM-1 on respiratory after viral respiratory illness.14 25 This may be epithelial cells.18 19 The infectious chlamydial due to cholinergic hyperresponsiveness or particle is the elementary body that attaches immunological reactions.14 28–30 itself to and enters a susceptible cell where it Chlamydia pneumoniae can cause prolonged Department of changes to the larger metabolically active acute bronchitis with wheezing6153132 and Infectious Diseases, reticulate body.20 Viable chlamydiae may be Hahn and coworkers6 found that nine (47%) of Marselisborg Hospital, DK-8000 Århus C, present at the site of infection and induce an 19 patients with acute C pneumoniae infection 20 Denmark inflammatory response. M pneumoniae at- had bronchospasm during their respiratory ill- P Andersen taches to ciliated epithelial cells by a specialised ness. They also found that 29% of 71 adults Pathogenesis of lower respiratory tract infections 303 with C pneumoniae antibody titres above 32 had patients43 and it has been suggested that they or developed asthmatic bronchitis after a respi- have a possible role in the pathogenesis. How- ratory illness compared with only 7% of a ever, it should be borne in mind that antibod- Thorax: first published as 10.1136/thx.53.4.302 on 1 April 1998. Downloaded from matched control group. In another study33 C ies could result from stimulation with cross pneumoniae could be isolated from the naso- reacting antigens and that a number of pharynx of 11% of asthmatic children with an diVerent antibodies are found in patients with acute episode of wheezing but in only 4.9% of M pneumoniae infection.44 a control group. Thus, infection with C pneumoniae can trigger acute episodes of BRONCHIOLITIS wheezing in asthmatic children and Allegra and Bronchiolitis is an acute infection of the small coworkers34 found a similar association in bronchi and bronchioles in children below the adults. C pneumoniae infection may predispose age of 2–3 years. Some authors may include to bronchospasm during subsequent infections older children and use the term “wheezing with other respiratory pathogens, or a pro- associated respiratory infection”.1 RSV is the longed infection and exposure to C pneumoniae major cause of bronchiolitis, accounting for may explain a protracted illness.32 Similar to 45–75% of the cases, while parainfluenza virus findings in some viral respiratory tract infec- is responsible for 15–30%. Rhinovirus, adeno- tions with wheezing,29 30 specific IgE antibodies virus, and influenza virus have each been could be demonstrated in C pneumoniae isolated in 3–10% and M pneumoniae has been infection.35 IgE antibodies were detected by an found in a small percentage.1230 Serological immunoblotting technique in 85% of 14 asth- evidence of C trachomatis and C pneumoniae matic children aged 5–15 years with culture infection in bronchiolitis has been described in proven C pneumoniae respiratory infection and a few cases.38 Legionella species may cause also in 18–22% of culture negative asthmatics inflammation in bronchioles in connection and asymptomatic children.35 Antibodies to a with pneumonia,45 but a clinical syndrome of 98 kD protein that seem to be C pneumoniae bronchiolitis due to these bacteria has not been specific were most commonly recognised.36 reported. Some serum samples also reacted with epitopes RSV may initially replicate in the epithelium present in C trachomatis, but the pattern of of the upper respiratory airways and it then reactivity was diVerent with the two species.35 subsequently spreads downwards along the These findings suggest that type 1 allergy may epithelium of the respiratory tract, mostly by be implicated in the pathogenesis of C pneumo- cell to cell transfer. The bronchiolar epithelium niae infection. The role of C trachomatis as a is colonised by virus and necrosis may occur. respiratory pathogen after the neonatal period Peribronchial inflammation with predomi- is controversial. C trachomatis was isolated from nantly mononuclear cells and oedema is seen. pharyngeal swabs in seven of 20 children with Thick plugs composed of cell debris and fibrin http://thorax.bmj.com/ wheezing37 and serological evidence of acute are found, and they may lead to partial infection with C trachomatis was found in obstruction of the bronchioles, resulting in air 19.2% of Argentinian children aged 1–18 trapping.46 This obstruction is probably the months with acute lower respiratory tract most important feature of acute bronchiolitis. infection.38 On the other hand, C trachomatis The pathological process may progress and could not be isolated from 48 children newly involve the alveolar walls leading to interstitial admitted to an asthma clinic in the UK,39 and pneumonia. During recovery the bronchiolar Hahn and coworkers6 did not find any correla- epithelium regenerates within a few days. The tion between C trachomatis antibody titres and elastic and muscular tissues are not damaged on September 27, 2021 by guest. Protected copyright. wheezing in children and adults with lower res- and the bronchial tree should recover piratory tract infection. Thus, the role of Ctra- completely.46 chomatis and C psittaci in bronchitis and In RSV bronchiolitis the pathogenesis of the wheezing is still undetermined and further inflammatory process may involve an abnormal studies are needed. immunological response. Children vaccinated Mycoplasma pneumoniae infection may result against RSV with a formalin inactivated in bronchitis about 30 times more often than it vaccine developed an antibody response with- causes pneumonia17 and it may be
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