Viral, Bacterial, and other Health Conditions

 

General             Viral      Bacterial           Other Health Conditions

General

 

Author(s): Marshall GD Jr ; Agarwal SK 
Affiliation: Division of Allergy and Clinical Immunology, University of Texas Houston Medical School, Houston, USA.

Title: Stress, immune regulation, and immunity: applications for asthma. Source: Allergy Asthma Proc (Allergy and asthma proceedings : the official journal of regional and state allergy societies.) 2000 Jul-Aug; 21(4): 241-6

Abstract: The neuroendocrine mediators reach the cells of the immune system either through the peripheral circulation or through direct innervation of lymphoid organs. Primary and secondary lymphoid organs are innervated by sympathetic nerve fibers. Lymphocytes and monocytes express receptors for several stress hormones, including CRH, ACTH, cortisol, norepinephrine, and epinephrine. Therefore, it is reasonable to conclude that the neuroendocrine hormones released during a stressful event could alter immune function and subsequently alter the course of immune-based diseases. The impact of psychological stress on immune function has been the subject of extensive research efforts. Using a variety of models from largely healthy humans undergoing various forms of natural and experimental stress models, stress has been associated with suppression of NK activity, mitogen- and antigen-induced lymphocyte proliferation and in vitro production of IL-2 and IFN-gamma. Psychological stress is also associated with a higher rate of in vivo hypoergy to common recall-delayed type hypersensitivity antigens. These studies have suggested that psychological stress suppresses various components of CMI responses. Also, data suggest that chronic stress does not simply suppress the immune system, but induces a shift in the type-1/type-2 cytokine balance toward a predominant type-2 cytokine response. Such a change would favor the inflammatory milieu characteristic of asthma and allergic diseases. Recent studies using well-controlled teenage asthmatic subjects demonstrated immunological changes (decreased NK cell cytotoxicity and cytokine alterations) in response to exam stress. These immune alterations are consistent with a cytokine milieu that could potentially worsen asthma. However, there were no changes in peak flow rates, self-report asthma symptoms, or medication use. The lack of correlation between stress and asthma symptoms may have been related to the timing of the visits in relation to the stressor, the duration of the stressor, disease severity, or a lack of accurate self-report data. Alternatively, stress-mediated exacerbations of asthma may require multiple alterations by stress, including cytokine dysregulation or vagal-mediated airway hyperresponsiveness. The rationale for stress management in asthma is based upon the notion that stress causes a change in immune balance that would favor asthma activity in susceptible individuals. This immune imbalance can be found in TH1/TH2 cytokine changes that occur with stress. Although it has not yet been demonstrated that stress can cause or directly influence the development of asthma, it is interesting to note that both the incidence and prevalence of asthma continue to increase and are higher in urban than in rural areas. Among other differences is the well-appreciated higher chronic stress levels associated with urban living.

 

Viral

General             Viral      Bacterial           Other Health Conditions

 

Author(s): Gern JE ; Busse WW 
Affiliation: Department of Pediatrics, University of Wisconsin Medical School, Madison, USA.

Title: The role of viral infections in the natural history of asthma. Source: J Allergy Clin Immunol (The Journal of allergy and clinical immunology.) 2000 Aug; 106(2): 201-12

Abstract: Viral infections have been related to the inception of recurrent wheezing illnesses and asthma in infants and are probably the most frequent cause of exacerbations of established disease in older children and adults. The well-recognized clinical effects of viral infections are mainly caused by virus-induced immune responses. Clinical studies of natural and experimentally induced viral infections have led to the identification of mechanisms of inflammation that could be involved in producing airway obstruction and lower airway symptoms. In addition, host factors that are associated with more vigorous viral replication or severe clinical illness are beginning to be identified. Advances in molecular virology and our understanding of immune responses to viral infections may lead to the development of new strategies for the prevention and treatment of virus-induced respiratory disorders.

 

 

Author(s): Gern JE ; Lemanske RF Jr 
Affiliation: Department of Pediatrics, University of Wisconsin Medical School, Madison, WI 53792, USA. gern@medicine.wisc.edu
Title: Infectious triggers of pediatric asthma. Source: Pediatr Clin North Am (Pediatric clinics of North America.) 2003 Jun; 50(3): 555-75, vi

Abstract: Respiratory infections can cause wheezing illnesses in children of all ages and also can influence the causation and disease activity of asthma. For years it has been recognized that respiratory syncytial virus infections often produce the first episode of wheezing in children who go on to develop chronic asthma. More recently, it has been proposed that repeated infections with other common childhood viral pathogens might help the immune system develop in such a way as to prevent the onset of allergic diseases and possibly asthma. In addition to the effects of viral infections, infections with certain intracellular pathogens, such as chlamydia and mycoplasma, may cause acute and chronic wheezing in some individuals, whereas common cold and acute sinus infections can trigger acute symptoms of asthma. In this article, the epidemiologic, mechanistic, and treatment implications of the association between respiratory infections and asthma are discussed.

 

 

Author(s): Yamaya M ; Sasaki H 
Affiliation: Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan. yamaya@geriat.med.tohoku.ac.jp

Title: Rhinovirus and asthma. Source: Viral Immunol (Viral immunology.) 2003; 16(2): 99-109

Abstract: Rhinoviruses (RVs) cause the majority of common colds, which often provoke wheezing in patients with asthma. The precise mechanisms responsible for the RV infection-induced exacerbations of bronchial asthma are still uncertain. However, several reports reveal airway hyperresponsiveness, increases in chemical mediators in airway secretions such as kinin and histamine, and airway inflammation in patients with bronchial asthma after RV infection. RV infection induces an accumulation of inflammatory cells in airway mucosa and submucosa including neutrophils, lymphocytes and eosinophils. RV affects the barrier function of airway epithelial cells, and activates the airway epithelial cells and other cells in the lung to produce pro-inflammatory cytokines, including various kinds of interleukins, GM-CSF and RANTES, and histamine. RV also stimulates the expression of intercellular adhesion molecule-1 (ICAM-1) and low-density lipoprotein receptors in the airway epithelium, receptors for major and minor RVs. On the other hand, RV infection is inhibited by treatment with soluble ICAM-1, and by reduction of ICAM-1 expression in the airway epithelial cells after treatment with erythromycin. Both soluble ICAM-1 and erythromycin were reported to reduce the frequency of common colds. Here, we review the pathogenesis and management of RV infection-induced exacerbation of bronchial asthma.

 

 

Author(s): Jacoby DB 
Affiliation: Johns Hopkins School of Public Health, 615 N Wolfe St, Room W7006, Baltimore, MD 21205, USA. djacoby@jhmi.edu
Title: Virus-induced asthma attacks. Source: JAMA (JAMA : the journal of the American Medical Association.) 2002 Feb 13; 287(6): 755-61

Abstract: Viral respiratory tract infections are a common cause of asthma attacks. Study of this phenomenon has revealed multiple mechanisms and contributed to understanding of the increase in airway inflammation and bronchoconstriction observed in this context. Changes in the neural control of the airways contribute to bronchoconstriction, which is reflected in an increased efficacy of anticholinergic medications during acute asthma attacks. The ability to prevent or treat viral respiratory tract infections is currently limited. However, as more effective antiviral treatments and vaccines become available, such therapies are likely to be effective in patients with asthma. Clinical management of this problem is illustrated in this article by the case of a 40-year-old woman with history of mild asthma who was admitted to an intensive care unit with severe bronchospasm and an upper respiratory tract infection.

 

 

Author(s): Welliver RC 
Affiliation: Department of Pediatrics, State University of New York at Buffalo, The Children's Hospital of Buffalo, USA.

Title: Immunologic mechanisms of virus-induced wheezing and asthma. Source: J Pediatr (The Journal of pediatrics.) 1999 Aug; 135(2) Pt 2: 14-20

Abstract: Viral infections are a common cause of wheezing at all ages. In addition, it has been suggested that viral infections can induce a long-term asthma diathesis. Because asthma is increasingly understood to be an inflammatory disease, there is great interest in the immunologic mechanisms that may underlie virus-induced wheezing. Viral infections may induce inflammatory responses that closely resemble those characteristic of asthma, including airway infiltration with lymphocytes and eosinophils and release of mediators of airway obstruction. Certain viruses preferentially enhance pre-existing inflammatory responses in atopic individuals. Alternatively, viral infections may induce an altered reactivity favoring the expression of atopy. Finally, immunologic responses to viral infections may serve only as markers of the subsequent development of atopy.

 

 

Author(s): Grünberg K ; Sterk PJ 
Affiliation: Department of Pulmonology, Leiden University Medical Center, The Netherlands.

Title: Rhinovirus infections: induction and modulation of airways inflammation in asthma. Source: Clin Exp Allergy (Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.) 1999 Jun; 29 Suppl 2: 65-73

Abstract: There is renewed interest in the role of respiratory virus infections in the pathogenesis of asthma and in the development of exacerbations in pre-existing disease. This is due to the availability of new molecular and experimental tools. Circumstantial evidence points towards a potentially causative role as well as to possibly protective effects of certain respiratory viruses in the cause of allergic asthma during early childhood. In addition, it now has become clear that exacerbations of asthma, in children as well as adults, are mostly associated with respiratory virus infections, with a predominant role of the common cold virus: rhinovirus. Careful human in vitro and in vivo experiments have shown that rhinovirus can potentially stimulate bronchial epithelial cells to produce pro-inflammatory chemokines and cytokines, may activate cholinergic- or noncholinergic nerves, increase epithelial-derived nitric oxide synthesis, upregulate local ICAM-1 expression, and can lead to nonspecific T-cell responses and/or virus-specific T-cell proliferation. Experimental rhinovirus infections in patients with asthma demonstrate features of exacerbation, such as lower airway symptoms, variable airways obstruction, and bronchial hyperresponsiveness, the latter being associated with eosinophil counts and eosinophilic cationic protein levels in induced sputum. This suggests that multiple cellular pathways can be involved in rhinovirus-induced asthma exacerbations. It is still unknown whether these mechanisms are a distinguishing characteristic of asthma. Because of the limited effects of inhaled steroids during asthma exacerbations, new therapeutic interventions need to be developed based on the increasing pathophysiological knowledge about the role of viruses in asthma.

 

 

Author(s): Macek V ; Dakhama A ; Hogg JC ; Green FH ; Rubin BK ; Hegele RG 
Affiliation: McDonald Research Laboratories, St Paul's Hospital, Vancouver, Canada.

Title: PCR detection of viral nucleic acid in fatal asthma: is the lower respiratory tract a reservoir for common viruses? Source: Can Respir J (Canadian respiratory journal : journal of the Canadian Thoracic Society.) 1999 Jan-Feb; 6(1): 37-43

Abstract: BACKGROUND: There is indirect evidence implicating viral respiratory tract infections in the pathogenesis of fatal asthma. However, it is unknown whether viruses are present within the lower respiratory tract in fatal asthma. OBJECTIVES: To apply a nine-virus polymerase chain reaction (PCR) panel to postmortem specimens of lower airway secretions and compare the prevalence of viral nucleic acid among patients who died of asthma, asthmatic patients who died of other causes and persons who died without lung disease. PATIENTS AND METHODS: Postmortem specimens of lower airway secretions from patients who died of asthma (fatal asthma [n=10]), asthmatic patients who died of other causes (n=4) and nonasthma controls (n=6) underwent PCR for nine common respiratory viruses. The prevalence of each virus was compared among the three groups. RESULTS: PCR was positive for at least one virus in 19 of 20 cases, and multiple viruses were detected in 14 of 20 cases. The prevalence of each virus was similar in the three groups studied. CONCLUSIONS: In fatal asthma, lower airway secretions do not show a specific pattern of viral nucleic acid. Intriguingly, these results suggest that the lower respiratory tract may act as a potential reservoir for common respiratory viruses.

 

 

Author(s): Isaacs D ; Joshi P 
Affiliation: Department of Immunology and Infectious Diseases, The Children's Hospital at Westmead, University of Sydney, NSW. davidi@chw.edu.au

Title: Respiratory infections and asthma. Source: Med J Aust (The Medical journal of Australia.) 2002 Sep 16; 177 Suppl: S50-1

Abstract: What we know: Respiratory viral infections caused by rhinoviruses, coronaviruses, influenza, parainfluenza and respiratory syncytial viruses (RSVs) are important triggers of asthma attacks. Mycoplasma and Chlamydia infections can also provoke asthma attacks, although less commonly. RSV infections probably do not cause asthma, but are potent triggers of wheezing, with the result that RSV infection often reveals underlying asthma in children. RSV infection does not cause atopy. Bacterial respiratory infections in infancy appear to protect against later atopy. What we need to know: Does RSV infection in infancy alter a child's T(H)1/T(H)2 responses to later infections with other respiratory pathogens? What are the mechanisms (immunological or mechanical) by which respiratory pathogens cause wheezing? What is the role of respiratory infections in exacerbations of asthma? Can epidemiology shed light on this? Do viruses such as RSV cause asthma or uncover underlying asthma? Do children respond differently to RSV than to other viruses? Does atopy affect those responses? Do bacterial respiratory infections truly protect against future atopy?

 

 

Author(s): Van Bever HP ; Chng SY ; Goh DY 
Affiliation: Pediatric Allergy and Immunology Division, National University of Singapore, Singapore.

Title: Childhood severe acute respiratory syndrome, coronavirus infections and asthma.

Source: Pediatr Allergy Immunol (Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.) 2004 Jun; 15(3): 206-9
 

Abstract: Van Bever HP, Chng SY, Goh DY. Childhood severe acute respiratory syndrome, coronavirus infections and asthma. Pediatr Allergy Immunol 2004: 15: 206-209.
Copyright 2004 Blackwell MunksgaardSevere acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus. Children appear to be less susceptible to the SARS coronavirus, although the other non-SARS coronaviruses can cause respiratory infections in adults and in children of all ages. The exact reasons as to why SARS preferentially affects adults, and not children, are still unknown. Many hypotheses exist and need to be explored. During the outbreak of SARS, there did not appear to be an increase in asthma exacerbations in children.

 

 

Author(s): Schwarze J ; Schauer U 
Affiliation: Children's Clinic, St Josef-Hospital, 44791 Bochum, Germany. j.schwarze@ic.ac.uk

Title: Enhanced virulence, airway inflammation and impaired lung function induced by respiratory syncytial virus deficient in secreted G protein. Source: Thorax (Thorax.) 2004 Jun; 59(6): 517-21


Abstract: BACKGROUND: Respiratory syncytial virus (RSV) infection can cause bronchial hyperresponsiveness and asthma exacerbations. In mice it results in airway inflammation and airway hyperresponsiveness. Since viral factors influencing these responses are not well defined, a study was undertaken to investigate the role of secreted G protein of human RSV in determining virulence, inflammatory responses, and changes in lung function. METHODS: BALB/c mice were infected with a spontaneous mutant of RSV deficient in secreted G protein (RSV-DeltasG) or with wild type RSV (RSV-WT). Viral titres, numbers of pulmonary inflammatory cells, and concentrations of interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 in bronchoalveolar lavage (BAL) fluid were determined. Airway function was assessed at baseline and following methacholine provocation using barometric whole body plethysmography. RESULT: Following infection with RSV-DeltasG, viral titres were increased 50-fold compared with RSV-WT. Influx of eosinophils and macrophages to the lung and concentrations of IFN-gamma and IL-10 in BAL fluid were also significantly higher following infection with RSV-DeltasG. Airway function, both at baseline and after methacholine provocation, was significantly decreased following infection with RSV-DeltasG compared with RSV-WT. CONCLUSION: Secreted G protein is likely to be a regulatory factor in RSV infection limiting infectivity of the virus, inflammatory responses in the lungs, and reduction in lung function.

 

 

Author(s): Lee AM ; Fryer AD ; van Rooijen N ; Jacoby DB 
Affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.

Title: Role of macrophages in virus-induced airway hyperresponsiveness and neuronal M2 muscarinic receptor dysfunction. Source: Am J Physiol Lung Cell Mol Physiol (American journal of physiology. Lung cellular and molecular physiology.) 2004 Jun; 286(6): L1255-9

Abstract: Viral infections exacerbate asthma. One of the pathways by which viruses trigger bronchoconstriction and hyperresponsiveness is by causing dysfunction of inhibitory M(2) muscarinic receptors on the airway parasympathetic nerves. These receptors normally limit acetylcholine (ACh) release from the parasympathetic nerves. Loss of M(2) receptor function increases ACh release, thereby increasing vagally mediated bronchoconstriction. Because viral infection causes an influx of macrophages into the lungs, we tested the role of macrophages in virus-induced airway hyperresponsiveness and M(2) receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperresponsive to electrical stimulation of the vagus nerves but not to intravenous ACh, indicating that hyperresponsiveness was due to increased release of ACh from the nerves. In addition, the muscarinic agonist pilocarpine no longer inhibited vagally induced bronchoconstriction, indicating M(2) receptor dysfunction. Treating animals with liposome-encapsulated dichloromethylene-diphosphonate depleted macrophages as assessed histologically. In these animals, viral infection did not cause airway hyperresponsiveness or M(2) receptor dysfunction. These data suggest that macrophages mediate virus-induced M(2) receptor dysfunction and airway hyperresponsiveness.

 

 

Author(s): Akazawa S ; Matsuse H ; Saeki S ; Machida I ; Kondo Y ; Tsuchida T ; Kohno S 
Affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

Title: [Two cases of asthmatic exacerbation caused by parainfluenza virus 3 infection] Source: Nihon Kokyuki Gakkai Zasshi (Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society.) 2004 Apr; 42(4): 353-6

Abstract: Although viral respiratory tract infections are considered to be the most frequent causes of asthmatic exacerbation, respiratory viruses can rarely be detected in the adult population. We describe 2 cases, in a 43-yr-old man with severe atopic asthma and in a 69-yr-old man with moderate non-atopic asthma. After the onset of nasal discharge, sore throat and fever, the asthma had become exacerbated in both cases during the summer of 2002. In both cases, parainfluenza virus (PIV) 3 viral RNA could be detected from oral gargling by RT-PCR, and the serum viral antibody titer against PIV 3 increased significantly. These cases were therefore diagnosed as undergoing asthmatic exacerbation caused by PIV 3 infection and were successfully treated with systemic steroids. During summer, 2002, in our outpatient clinic, PIV 3 infection was demonstrated in approximately half of the asthmatic exacerbations associated with upper respiratory symptoms, including the present cases. Collectively, PIV 3 seems to represent an important viral cause of asthma exacerbation in summer.

 

 

Author(s): Peebles RS Jr 
Affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.

Title: Viral infections, atopy, and asthma: is there a causal relationship? Source: J Allergy Clin Immunol (The Journal of allergy and clinical immunology.) 2004 Jan; 113(1) Suppl: S15-8

Abstract: Respiratory syncytial virus (RSV) remains the chief cause of hospitalization for lower respiratory tract illnesses in both infants and young children, and can produce severe outcomes. In addition, several studies have suggested that infants in whom RSV bronchiolitis develops may have recurrent wheezing and asthma later in childhood. Further complicating the picture is the question of whether there is a link between RSV infection in infancy and the development of atopy later in childhood. This review will discuss existing data on RSV infection and respiratory complications later in life, as well as the link between RSV and allergic disease.

 

 

Author(s): Peebles RS Jr ; Hartert TV 
Affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.

Title: Respiratory viruses and asthma. Source: Curr Opin Pulm Med (Current opinion in pulmonary medicine.) 2000 Jan; 6(1): 10-4

Abstract: Viral infections have become increasingly recognized as a significant cause of asthma exacerbations, mainly because of improved viral detection techniques. Unfortunately, the ability to specifically treat viral infections and to limit the asthma morbidity associated with these agents has not kept pace with diagnostic technology. This article focuses on current concepts of the epidemiology of viruses in asthma exacerbations, investigations studying the physiologic and immunologic consequences of viral infection, and potential therapies to minimize virally-induced airway hyperresponsiveness. To impact this significant health problem, researchers must definitively ascertain the mechanisms by which viruses induce airway reactivity and must develop rational, safe approaches to prevent the consequences of viral infection in the patient with asthma.

 

 

Author(s): Hogg JC 
Affiliation: UBC Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada. uhogg@mrl.ubc.ca
Title: Childhood viral infection and the pathogenesis of asthma and chronic obstructive lung disease. Source: Am J Respir Crit Care Med (American journal of respiratory and critical care medicine.) 1999 Nov; 160(5) Pt 2: S26-8

Abstract: Many epidemiologic studies have implicated childhood respiratory infections as an independent risk factor for the subsequent development of persistent asthma and chronic obstructive pulmonary disease (COPD). The majority of these childhood infections are viral in origin, and great strides are being made in understanding their pathogenesis at the molecular level. Some viruses, such as respiratory syncytial virus-a common cause of childhood bronchiolitis-stimulate the helper T cell type 2 (Th2) pattern of immune responses associated with allergic inflammation. Other viruses, such as adenovirus, appear to persist as latent infections in the airways of patients with COPD, and adenoviral E1A protein is capable of amplifying host genes, possibly including those involved in cigarette smoke-induced lung inflammation. Studies of the chronic, low-grade peripheral lung inflammation caused by adenoviral infection of guinea pigs will enable examination of the possibility that latent infection may induce resistance to the antiinflammatory actions of corticosteroids. Studies of the molecular mechanisms of viral infections of the airways could provide important insights into the nature of the inflammatory process involved in asthma and COPD. Hogg JC. Childhood viral infection and the pathogenesis of asthma and chronic obstructive lung disease.

 

 

Author(s): Allegra L ; Blasi F ; Centanni S ; Cosentini R ; Denti F ; Raccanelli R ; Tarsia P ; Valenti V 
Affiliation: Institute of Respiratory Diseases, University of Milan, Italy.

Title: Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection. Source: Eur Respir J (The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology.) 1994 Dec; 7(12): 2165-8

Abstract: Respiratory infections precipitate wheezing in many asthmatic patients and may be involved in the aetiopathogenesis of asthma. Several studies have demonstrated that viral infections may provoke asthma. Bacterial infections seem to play a minor role. However, Chlamydia pneumoniae has been recently reported as a possible cause of asthma. The aim of the present study was to evaluate the role of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma were studied. Acute and convalescent (> or = 3 weeks) serological determination of antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila were performed by means of immunofluorescence tests. C. pneumoniae specific antibodies were detected by two microimmunofluorescence tests using a specific antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab specimens were also obtained for C. pneumoniae identification. Samples for bacterial culture were obtained in patients with productive cough (15 out of 74 patients). Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

 

 

Author(s): von HL 
Affiliation: The Finnish Lung Health Association, Helsinki. leena.vonhertzen@filha.fi

Title: Role of persistent infection in the control and severity of asthma: focus on Chlamydia pneumoniae. Source: Eur Respir J (The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology.) 2002 Mar; 19(3): 546-56

Abstract: Conventional risk factors have been unable to explain most of the substantial increase in the prevalence of asthma observed in many countries during the last few decades. Much attention has been directed at the "hygiene hypothesis", the apparent inverse relationship between intense systemic childhood infections and the subsequent development of asthma and atopy. However, it is not only the absence or scarcity of infections, but the prolonged presence of certain microorganisms in the lungs that may be involved in the development of asthma. Accumulating evidence suggests that Chlamydia pneumoniae, an intracellular ubiquitous pathogen with an innate propensity to persist and cause chronic infections, may be associated with asthma. This microorganism can achieve a state of "latency" in which it is viable but dormant and does not multiply. During this state, however, chlamydia continues to synthesize the "stress" protein, a 60-kDa heat shock protein (hsp60). This protein is able to elicit a strong host inflammatory response at sites of its production and appears to be involved in tissue injury and scarring processes. As inflammation has been found to be present in almost all asthmatics, whatever the severity and aetiology of the disease, inhaled glucocorticoids now have an established position in the treatment of early stages. However, corticosteroids negatively affect many aspects of cell-mediated immunity and favour the shift from a T-helper-1-type response towards a T-helper-2-type response. Corticosteroids may thus severely deteriorate the host's ability to eradicate an intracellular pathogen, such as Chlamydia pneumoniae, which requires a properly functioning cell-mediated (T-helper-1-type) immune response to be cleared. These drugs are also able to reactivate persistent Chlamydia to an active growth phase, which, by increasing the production of pro-inflammatory cytokines at the site of infection, can further amplify inflammation in the airways of patients with asthma.

 

 

Author(s): Gern JE 
Affiliation: Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin 53792-9988, USA.

Title: Rhinovirus respiratory infections and asthma. Source: Am J Med (The American journal of medicine.) 2002 Apr 22; 112 Suppl 6A: 19S-27S

Abstract: Viral infections, particularly respiratory illnesses caused by rhinovirus, are the most common cause of asthma exacerbations in children and contribute in large part to asthma morbidity in adults. Epidemiologic studies and increasingly sophisticated viral detection methodologies have helped to define the role of rhinovirus as a potential causative agent in asthma exacerbations. Rhinovirus-induced lung disease is multifaceted and can be characterized in terms of a variety of physiologic, immunologic, and viral processes. The precise direct and indirect mechanisms of viral contribution to exacerbations must still be elucidated. Understanding them will have an impact on the design of future treatment modalities.

 

 

Author(s): Martin RJ ; Kraft M ; Chu HW ; Berns EA ; Cassell GH 
Affiliation: Department of Medicine, National Jewish Medical and Research Center and The Pulmonary and Critical Care Division, University of Colorado Health Sciences Center, 1400 Jackson St., Denver, CO 80206, USA.

Title: A link between chronic asthma and chronic infection. Source: J Allergy Clin Immunol (The Journal of allergy and clinical immunology.) 2001 Apr; 107(4): 595-601

 Abstract: BACKGROUND: Asthma is a prevalent disease with marked effects on quality of life and economic societal burden. However, the cause of asthma and its pathophysiology are not completely defined. Recently, the possibility that chronic infection may play a role has been suggested. OBJECTIVE: We sought to define the association between Mycoplasma and Chlamydia species and chronic asthma. METHODS: We performed a comparison study of asthmatic patients and normal control subjects. Fifty-five patients with chronic stable asthma were compared with 11 normal control subjects by using PCR, culture, and serology for Mycoplasma species, Chlamydia species, and viruses from the nasopharynx, lung, and blood. Bronchoalveolar lavage cell count and differential, as well as tissue morphometry, were also evaluated. Computer-generated scoring for the degree of chronic sinusitis in asthmatic patients was additionally evaluated. RESULTS: Thirty-one of 55 asthmatic patients had positive PCR results for Mycoplasma (n = 25) or Chlamydia species (n = 6), which were mainly found on lung biopsy specimens or in lavage fluid. Only 1 of 11 normal control subjects had positive PCR results for Mycoplasma species. The distinguishing phenotype between asthmatic patients with positive and negative PCR results was the significantly greater number of tissue mast cells in the group with positive results. CONCLUSION: A significant number of patients with chronic stable asthma demonstrate the presence of Mycoplasma species, Chlamydia species, or both in their airways, with the distinguishing feature of increased mast cell number. These findings need further delineation but may help us to understand the pathophysiology of asthma and new treatment options.

 

 

Author(s): Mygind N 
Affiliation: Dept of Respiratory Diseases, University Hospital of Aarhus, DK-8000 Aarhus, Denmark.

Title: The common cold as a trigger of asthma. Source: Monaldi Arch Chest Dis (Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Universita di Napoli, Secondo ateneo.) 2000 Dec; 55(6): 478-83

Abstract: The common cold is a viral disease with predominant symptoms from the upper airways. Rhinovirus is the most important common cold virus, and rhinovirus infection is predominantly transmitted by direct contact (nasal secretion-hand (object)-hand-mucous membrane in eye and nose). The viral disease results in the release of IL-8 from nasal epithelial cells, causing a neutrophil-dominated inflammation in the nose. The biochemical mediators, causing nasal symptoms, have not yet been identified. A common cold is the most important cause of exacerbations of asthma in children and also in adults. The rhinovirus infection induces airway inflammation, bronchial hyperresponsiveness and asthma symptoms. However, the mode of action of the virus-induced inflammation on the asthma disease is poorly understood. As a routine, physicians give oral corticosteroid and increase the dosage of inhaled corticosteroid during a common cold-induced exacerbation of asthma, but there do not seem to be any placebo-controlled trials in support of this practice.

 

Bacterial

General             Viral      Bacterial           Other Health Conditions

 

 

Author(s): Kraft M 
Affiliation: Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, USA. kraftm@njc.org

Title: The role of bacterial infections in asthma. Source: Clin Chest Med (Clinics in chest medicine.) 2000 Jun; 21(2): 301-13

Abstract: In summary, bacterial organisms are clinically relevant contributors to asthma exacerbations, and have received much less attention than viruses in this process. Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis have been linked to asthma exacerbations, particularly when sinusitis is present. Treatment therefore should be directed toward these organisms if a bacterial cause is suspected. The atypical bacteria--specifically, C. pneumoniae and M. pneumoniae--deserve special attention. Data suggest a link between these organisms and the exacerbation of asthma, as well as suggest that these organisms may be causative in asthma development. The existing data are not conclusive, but are suggestive enough to drive studies evaluating them as a possible mechanism in asthma pathogenesis. An animal model evaluating M. pneumoniae and C. pneumoniae would be ideal, but at present no model exists in which chronic infection with these organisms results in bronchial hyperresponsiveness. There is active work in this area, however. Alternative investigations include continued evaluation of these organisms by several modalities, including culture, serology, and PCR, along with evaluation of the host response. Many questions remain, but the ground is fertile for continued investigation.

 

 

Author(s): Virant FS 
Affiliation: Northwest Asthma & Allergy Center, University of Washington, 4540 Sand Point Way NE, Seattle, WA 98105, USA. fvirant@nwasthma.com

Title: Sinusitis and asthma: associated airway diseases. Source: Curr Allergy Asthma Rep (Current allergy and asthma reports.) 2001 May; 1(3): 277-81

Abstract: Sinusitis and asthma often coexist in patients. In fact, these airways disorders are similar histologically, with tissue eosinophils, increased glandular tissue, and edema. Medical or surgical therapy for sinusitis often greatly improves asthma, suggesting that sinusitis may exacerbate asthma. Possible mechanisms by which asthma could be worsened by sinus disease include neural reflex pathways and interference with the important nasal functions of heating, humidification, and filtration. Health professionals treating asthmatic patients should consider sinusitis as a possible underlying cause, in addition to other triggers (e.g., allergic rhinitis and gastroesophageal reflux disease).

 

 

Author(s): Gern JE 
Affiliation: University of Wisconsin Medical School, Madison, Wisconsin, USA.
Title: Viral and bacterial infections in the development and progression of asthma. Source: J Allergy Clin Immunol (The Journal of allergy and clinical immunology.) 2000 Feb; 105(2) Pt 2: S497-502
Additional Info: UNITED STATES
Standard No: ISSN: 0091-6749; NLM Unique Journal Identifier: 1275002 Language: English Abstract: Viral respiratory infections produce wheezing illnesses in patients of all ages. In infancy, infections with respiratory syncytial virus and parainfluenza virus are the major cause of bronchiolitis and croup, whereas infections with common cold viruses such as rhinoviruses are the principal triggers for wheezing in older children and adults with asthma. In addition to causing increased wheezing in asthma, there is mounting evidence that infections early in childhood can affect the development of the immune system and thereby modify the risk for the subsequent development of allergies and asthma. Both of these effects appear to be mediated by virus-induced immune responses. Early during the course of viral infection, resident cells in the airway are activated in an antigen-independent fashion, triggering antiviral responses but also activating and recruiting cells to the airway that could contribute to airway obstruction and respiratory symptoms. Virus-specific T- and B-cell responses may also have dual effects in the presence of preexisting airway inflammation. Finally, there is evidence of synergistic interactions between allergen- and virus-induced airway inflammation. It is likely that greater definition of mechanisms of virus-induced inflammation will provide therapeutic targets for the treatment and possibly the prevention of allergies and asthma.

 

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Affiliation: Veterans Affairs Hospital, Hines, Illinois 60141, USA.

Title: Gastroesophageal reflux disease and asthma. Source: J Clin Gastroenterol (Journal of clinical gastroenterology.) 2000 Apr; 30(3) Suppl: S9-30

Abstract: Gastroesophageal reflux (GER) and asthma occur together frequently. The relationship has been recognized for more than 2,000 years but has not been appreciated until recently. Attempts to determine the number of asthmatics that currently have GER (prevalence) have shown a higher-than-expected prevalence. Of the approximately 200 published studies on the relationship between GER and asthma, the true prevalence of GER in asthmatics, however, can be estimated from fewer than 20 of the studies. These studies, which comprise highly selected referred populations, are unlikely to reflect the overall population of patients with asthma. Nevertheless, the estimated prevalence of GER in asthmatics is between 60-80% in adults and 50-60% in children. No attempts have been made to determine the incidence of GER in asthmatics. To identify asthmatics who develop GER over time would be a formidable task, requiring decades of close follow-up of asthmatics who do not now have GER. Despite the lack of data on the incidence of GER, data on the prevalence raise an important issue: If the prevalence of GER in adult asthmatics is similar to the prevalence of GER in child asthmatics, what is the true incidence of GER? There are two potential answers: (1) all of the child asthmatics with GER grow up to become the adult asthmatics with GER (GER incidence = 0%); and (2) some child asthmatics with GER outgrow either the GER or the asthma; some adults with asthma develop GER while others with GER develop asthma (low, medium, or high incidence depending on the numbers). It is not unreasonable to suspect that some child asthmatics with GER become adult asthmatics with GER, and that children with GER who apparently "outgrow" their asthma surface later as adults with both asthma and GER. Because most children leave their pediatricians after adolescence, the information required to demonstrate continued asthma or GER is lost. As a result, the medical community sees two completely different populations, each with very similar conditions: childhood asthma with GER and adult asthma with GER. If the high prevalence of GER in asthmatics is clinically relevant, it should be readily explainable. We suggest that the GER/asthma relationship consists of a self-propagating situation whereby reflux aggravates asthma, which in turn induces further reflux. In the early course of the disease, asthma may not be apparent, as aspiration-induced pulmonary symptoms may occur very infrequently-perhaps once or twice a year. With time, however, aspiration may become more frequent, and the pulmonary tree may become hypersensitive. The individual may be diagnosed as having asthma. The pulmonary tree becomes increasingly hypersensitive, to a variety of stimuli. In such a scenario, the initial contribution of acid aspiration is no longer apparent, as the primary focus is on the asthma. In any individual patient, the emphasis may be placed on the GER if reflux symptoms predominate or on asthma if pulmonary symptoms predominate. The result is confusion over whether a patient with GER has asthma or whether a patient with asthma has GER. The unending debate about whether GER is a cause of the asthma or a result of the asthma becomes the focus of attention. At such a point, the question of whether GER exists in asthmatics or whether pulmonary symptoms exist in refluxers is irrelevant. For the individual patient, gastric contents refluxed into the pulmonary tree is an undesirable event, whether cause or effect, and it is up to the physician to determine how such events can be stopped.

 

 

Author(s): Wasowska-Królikowska K ; Toporowska-Kowalska E ; Krogulska A 
Affiliation: Clinic of Pediatric Gastroenterology and Allergology, Institute of Paediatrics, Medical University, Lódz, Poland.

Title: Asthma and gastroesophageal reflux in children. Source: Med Sci Monit (Medical science monitor : international medical journal of experimental and clinical research.) 2002 Mar; 8(3): RA64-71

Abstract: Gastroesophageal reflux (GER) is a factor often neglected in the etiopathogenesis of asthma. The estimated incidence of GER in asthmatic children reaches 50-60% and is higher than in the general population. GER may accompany typical symptoms: hoarseness, sore throat, thoracic pain, cough or wheezing. GER may not only aggravate the course of bronchial obstruction, but may also cause it, or trigger obstruction due to other factors. Asthma and GER coincidence has been acknowledged for many years. The paper presents a current review of studies concerning the relations between asthma and GER and attempts to establish, which is the cause and which is the result. The hypotheses how GER can lead to bronchial obstruction, and how obstruction can aggravate GER, are also presented. GER is believed to be a factor causing obstruction by: 1. an indirect mechanism - reflex theory, 2. a direct mechanism - reflux theory, and 3. a neuropeptide-mediated mechanism. The paper also presents diagnostic methods allowing to detect GER in asthmatics. A review of recent studies concerning the treatment of GER in asthmatics, both with pharmacological and surgical methods, is also included. Beneficial effect of antireflux therapy on the course of asthma has been emphasized. Therefore, antireflux therapy is recommended in all patients with concurrent asthma and GER, irrespective of severity of clinical GER symptoms, even in those with silent GER. The essential drugs used in the treatment of GER are proton pump inhibitors. Appropriately high dose level and appropriately long duration of the therapy should be taken into consideration.

 

 

Author(s): Anderson SD 
Affiliation: Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Title: Exercise-induced asthma and the use of hypertonic saline aerosol as a bronchial challenge. Source: Respirology (Respirology (Carlton, Vic.)) 1996 Sep; 1(3): 175-81

Abstract: Exercise induced asthma is a common complaint and the prevalence appears to be increasing worldwide. Once confined to the research domain of university teaching hospitals, the study of EIA has extended into the school playground, defence force establishments and sports institutions. Standardized protocols have been developed to study EIA in the laboratory and in the field. A surrogate challenge using eucapnic or isocapnic hyperventilation with dry air is becoming popular because it has advantages over exercise, at least for adults. The stimulus that leads the airways to narrow is caused by the inhalation of dry air during hyperventilation and exercise, during which water is evaporated from the airways in order to condition the inspired air. The mechanism whereby the airways narrow is thought to be due to the dehydrating effects of water loss, particularly in relation to its potential to cause the airways to become hyperosmolar. Mast cell mediators such as histamine and the leucotrienes are probably involved in EIA because specific antagonists reduce severity. As a result of the osmotic theory of EIA, studies were carried out to determine whether subjects with EIA were sensitive to the effects of increasing airway osmolarity by inhalation of hyperosmolar aerosols of sodium chloride. A challenge protocol using an aerosol of 4.5% sodium chloride, generated from an ultrasonic nebulizer, has been used to identify persons with asthma and to assess response to drug therapy. There are many similarities between responses to exercise, hyperventilation and hypertonic saline in the physiological and biochemical responses and the responses to drugs. Challenge with hypertonic saline is easier and cheaper to use because expensive equipment and a source of dry air is not required as with exercise or hyperventilation. The ability to obtain a dose-response curve rather than a single response and the ability to collect inflammatory cells at the same time make challenge with hypertonic saline an attractive technique to study patients suspected of having asthma.

 

Author(s): D'Alonzo GE ; Ciccolella DE 
Affiliation: Temple University Health Sciences Center, Philadelphia, PA 19140, USA.

Title: Nocturnal asthma: physiologic determinants and current therapeutic approaches. Source: Curr Opin Pulm Med (Current opinion in pulmonary medicine.) 1996 Jan; 2(1): 48-59

Abstract: Asthma has a tendency to destabilize at night in patients that are diurnaly active and try to sleep at night. As asthma worsens, the expression of this disease seems to increase at night. Additionally, nocturnal asthmatics have increased airway hyperresponsiveness and likely more active inflammation at night as compared with the daytime. Although the cause of nocturnal asthma cannot be completely explained, there do appear to be a variety of internal body circadian rhythms that play a role in this disease. Also, noncircadian rhythmic influences such as sleep, supine posture, snoring, and gastroesophageal reflux cannot be dismissed. Directing therapy, perhaps in unique ways, may be essential for the control of nocturnal asthma. Patients on inhaled corticosteroid therapy or nonsteroidal anti-inflammatory agents often persist in asthmatic disease expression at night. Long-acting bronchodilator therapy, either by inhalation or with sustained-release tablets, is often added to inhaled anti-inflammatory therapy for more complete 24-hour disease control. Using existing therapies but employing chronotherapeutic strategies is likely to improve the overall asthma management. By focusing on nocturnal asthma, we may be able to improve our understanding of this disease and more effectively control it over each 24-hour period.

 

Author(s): Kujala UM ; Sarna S ; Kaprio J ; Koskenvuo M 
Affiliation: Unit for Sports and Exercise Medicine, University of Helsinki, Finland.

Title: Asthma and other pulmonary diseases in former elite athletes. Source: Thorax (Thorax.) 1996 Mar; 51(3): 288-92

Abstract: BACKGROUND: The prevalence of asthma is rising and there are recent reports of increasing asthma rates among top level skiers and runners in the Nordic countries. METHODS: The lifetime occurrence of pulmonary diseases (asthma, chronic bronchitis, emphysema) and current bronchitis symptoms was compared in former elite male athletes (n = 1282) who represented Finland between 1920 and 1965 at least once in international competitions and controls (n = 777) who, at the age of 20, were classified as healthy and who responded to a questionnaire in 1985. The presence of disease and symptoms was identified from the questionnaire and, in the case of asthma, also from a nationwide reimbursable medication register. The death certificates of the subjects of our original cohort who died between 1936 and 1985 were also investigated to determine the cause of death. RESULTS: The occurrence of the pulmonary diseases was associated with age, smoking habits, occupational group, and a history of exposure to chemicals. After adjusting for these variables, athletes who participated in mixed sports (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.23 to 0.92) and power sports (OR 0.43, 95% CI 0.21 to 0.87) had lower odds ratios for emphysema, and endurance sports athletes had a lower odds ratio for the presence of at least one pulmonary disease (OR 0.53, 95% CI 0.28 to 0.98) when compared with controls. Athletes also tended to have fewer reimbursable medications for asthma and fewer current symptoms for chronic bronchitis. Between 1936 and 1985 two controls but none of the athletes died of asthma. CONCLUSIONS: The lifetime occurrence of asthma or other pulmonary diseases is not increased in former elite athletes, and exercise alone, even in a cold environment, did not appear to increase the prevalence of asthma, at least up to the mid 1980s.

 

Author(s): Giesbrecht GG ; Younes M 
Affiliation: Faculty of Physical Education and Recreation Studies, University of Manitoba, Winnipeg.

Title: Exercise- and cold-induced asthma. Source: Can J Appl Physiol (Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.) 1995 Sep; 20(3): 300-14

Abstract: Exercise- and cold-induced asthma are commonly recognized respiratory disorders. The asthmatic response includes several factors contributing to airway narrowing, and thus increased airway resistance. These include airway smooth muscle contraction, mucus accumulation, and bronchial vascular congestion as well as epithelial damage and vascular leakage. The etiology for these disorders is nonantigenic. The primary stimulus is probably a combination of airway cooling and drying (leading to hypertonicity of airway lining fluid). Symptoms generally do not occur during the stimulus period (e.g., exercise) itself. This protection may in part be due to increased catecholamine levels during exercise. The early phase response, which occurs 5 to 15 min poststimulus, may be mediated through a combination of (a) direct influences, (b) vagal reflexes triggered by airway sensory receptors, or (c) responses to mediator release. Spontaneous recovery occurs within 30 min to 2 hrs. There is usually a refractory period of about 1 to 2 hrs during which responses to further stimuli are attenuated. This may be due to depletion of histamine and other mediators. As well, prostaglandin release (mediated via LTD4 which is released during exercise) inhibits further airway narrowing. A late phase response has been reported 4 to 10 hrs poststimulus in some patients. These reactions are accompanied by a second release of histamine and other mediators that cause inflammatory responses and epithelial damage. However, the exercise dependence of this response is debated.

 

Author(s): Becker JM ; Rogers J ; Rossini G ; Mirchandani H ; D'Alonzo GE Jr 
Affiliation: Section of Allergy, Asthma and Immunology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, USA.

Title: Asthma deaths during sports: report of a 7-year experience. Source: J Allergy Clin Immunol (The Journal of allergy and clinical immunology.) 2004 Feb; 113(2): 264-7

 Abstract: BACKGROUND: Asthma mortality and the mortality of athletes during sports have been described separately in detail in the medical literature. However, asthma has not been reported as a cause of death in competitive athletes. OBJECTIVE: The object of this study was to raise the awareness of physicians, coaches, trainers, and parents that children and adults can have fatal asthma exacerbations during and immediately after participating in sports. METHODS: The Temple Sports Asthma Research Center identified athletes from 1993 until 2000 who died during or after sporting activity by using the nationwide Burrell's Information Service. Once a possible asthma-related sports death was identified, the autopsy report was requested from the coroner or medical examiner, and an attempt was made to contact the family. Contact with the family was limited to information about the death, medical history, sports involvement, and any medication usage by the person who had died. Secondary sources, including news reports, were used to confirm whether the subject died of asthma during or immediately after a sporting activity. RESULTS: Two hundred sixty-three possible cases were identified. Sixty-one deaths met the criteria for study inclusion. White deaths outnumbered black deaths by 2 to 1. Deaths among male subjects predominated. Most subjects were younger than the age of 20 years, with the most prevalent age group being between 10 to 14 years old. Fifty-one percent (18 of 35) of the competitive athletes had their fatal event while participating in organized sport, 14 in a practice situation and 4 deaths during a game or meet setting. Basketball and track were the 2 most frequent activities performed at the time of the fatal event. CONCLUSION: The subjects who had fatal asthma exacerbations were usually white male subjects between the ages of 10 and 20 years. Mild intermittent or persistent asthma by history was commonly identified. Sudden fatal asthma exacerbations occur in both competitive and recreational athletes and can be precipitated by sporting activity.