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Topic:Respiratory Disease

Respiratory disease in horses encompasses a range of conditions affecting the respiratory system, including the upper and lower airways. These diseases can result from various etiologies such as infectious agents, environmental factors, or genetic predispositions. Common respiratory conditions in horses include equine asthma, equine influenza, and strangles. Clinical signs often associated with respiratory disease in horses include coughing, nasal discharge, and labored breathing. Diagnostic approaches may involve endoscopy, imaging, and laboratory tests to assess the function and health of the respiratory tract. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, and management of respiratory diseases in equine populations.
Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.
Veterinary research    February 7, 2011   Volume 42, Issue 1 23 doi: 10.1186/1297-9716-42-23
Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP.Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EH...
Functional modelling of an equine bronchoalveolar lavage fluid proteome provides experimental confirmation and functional annotation of equine genome sequences.
Animal genetics    February 6, 2011   Volume 42, Issue 4 395-405 doi: 10.1111/j.1365-2052.2010.02158.x
Bright LA, Mujahid N, Nanduri B, McCarthy FM, Costa LR, Burgess SC, Swiderski CE.The equine genome sequence enables the use of high-throughput genomic technologies in equine research, but accurate identification of expressed gene products and interpreting their biological relevance require additional structural and functional genome annotation. Here, we employ the equine genome sequence to identify predicted and known proteins using proteomics and model these proteins into biological pathways, identifying 582 proteins in normal cell-free equine bronchoalveolar lavage fluid (BALF). We improved structural and functional annotation by directly confirming the in vivo expressio...
Evaluation of suitable reference genes for gene expression studies in bronchoalveolar lavage cells from horses with inflammatory airway disease.
BMC molecular biology    January 28, 2011   Volume 12 5 doi: 10.1186/1471-2199-12-5
Beekman L, Tohver T, Dardari R, Léguillette R.The stability of reference genes has a tremendous effect on the results of relative quantification of genes expression by quantitative polymerase chain reaction. Equine Inflammatory Airway Disease (IAD) is a common condition often treated with corticosteroids. The diagnosis of IAD is based on clinical signs and bronchoalveolar lavage (BAL) fluid cytology. The aim of this study was to identify reference genes with the most stable mRNA expression in the BAL cells of horses with IAD irrespective of corticosteroids treatment. Results: The expression stability of seven candidate reference genes (B2...
Influence of modified open lung concept ventilation on the cardiovascular and pulmonary function of horses during total intravenous anaesthesia.
The Veterinary record    January 26, 2011   Volume 167, Issue 26 1002-1006 doi: 10.1136/vr.c4172
Bringewatt T, Hopster K, Kästner SB, Rohn K, Ohnesorge B.The influence of a modified open lung concept (mOLC) on pulmonary and cardiovascular function during total intravenous anaesthesia (TIVA) in horses was evaluated. Forty-two warmblood horses (American Society of Anesthesiologists class 1 to 2), scheduled for elective surgery (mean [sd] weight 526 [65] kg, age 6.4 [5.4] years) were randomly divided into three groups: ventilation with mOLC, intermittent positive-pressure ventilation (IPPV), and spontaneous breathing. Premedication (0.8 mg/kg xylazine), induction (2.2 mg/kg ketamine and 0.05 mg/kg diazepam) and maintenance of anaesthesia with TIVA...
LC-MS/MS method for the simultaneous determination of clarithromycin, rifampicin and their main metabolites in horse plasma, epithelial lining fluid and broncho-alveolar cells.
Journal of pharmaceutical and biomedical analysis    January 22, 2011   Volume 55, Issue 1 194-201 doi: 10.1016/j.jpba.2011.01.019
Oswald S, Peters J, Venner M, Siegmund W.Clarithromycin (CLA) is a well established macrolide antibiotic which is frequently used in therapy of airway diseases in foals. It is extensively metabolized by CYP3A4 resulting in the antimicrobial active metabolite 14-hydroxyclarithromycin (OH-CLA). Rifampicin (RIF) is often comedicated to prevent resistance and augment therapy. RIF is a known inducer for metabolizing enzymes and transporter proteins. Therefore, comedication might bare the risks of pharmacokinetic drug interactions which were investigated in a clinical trial. As no adequate method to determine CLA, RIF and their main metabo...
Assessment of the impact of collection temperature and sampler design on the measurement of exhaled breath condensate pH in healthy horses.
Veterinary journal (London, England : 1997)    January 19, 2011   Volume 191, Issue 2 208-212 doi: 10.1016/j.tvjl.2010.12.013
Whittaker AG, Love S, Parkin TD, Duz M, Cathcart M, Hughes KJ.The pH measurement of exhaled breath condensate (EBC) may provide a non-invasive method of assessing the lower airways of horses but the methodology used may influence findings. The aim of this study was to investigate the effect of two sampling devices and three methods of condensation surface cooling (ethanol slush, -100°C; dry ice, -75°C; water ice, 0°C) on EBC pH. Each method was tested 30 times using six healthy ponies. Sample pH was determined before and after de-aeration with argon for 10 min. Sampler design was found to significantly affect pH. Samples collected as a liquid had a si...
Immunocytochemical detection of Rhodococcus equi in tracheal washes of foals.
Journal of comparative pathology    January 15, 2011   Volume 145, Issue 1 6-11 doi: 10.1016/j.jcpa.2010.11.014
Sonmez K, Gurel A, Takai S.The aim of the present study was to develop an immunocytochemical procedure for the early detection and demonstration of Rhodococcus equi in smears of tracheal aspirates taken from live foals in field conditions. Tracheal wash samples were collected from thoroughbred foals, aged 1-5 months and located in studs around Bursa and Istanbul, Turkey. Some foals were suspected of having R. equi infection on the basis of clinical examination (n=56) and others were unaffected control animals (n=54). Serum samples were also collected from each foal for testing for the presence of R. equi-specific antibo...
Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model.
Veterinary immunology and immunopathology    January 11, 2011   Volume 140, Issue 3-4 226-236 doi: 10.1016/j.vetimm.2010.12.008
Quintana AM, Landolt GA, Annis KM, Hussey GS.Our understanding of innate immunity within the equine respiratory tract is limited despite growing evidence for its key role in both the immediate defense and the shaping of downstream adaptive immune responses to respiratory disease. As the first interface to undergo pathogen invasion, the respiratory epithelium is a key player in these early events and our goal was to examine the innate immune characteristics of equine respiratory epithelia and compare them to an in vitro equine respiratory epithelial cell model cultured at the air-fluid interface (AFI). Respiratory epithelial tissues, isol...
Surveillance of equine respiratory viruses in Ontario.
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire    January 5, 2011   Volume 74, Issue 4 271-278 
Diaz-Mendez A, Viel L, Hewson J, Doig P, Carman S, Chambers T, Tiwari A, Dewey C.The objective of this project was to develop and implement an active surveillance program for the early and rapid detection of equine influenza viruses in Ontario. For this purpose, from October 2003 to October 2005, nasopharyngeal swabs and acute and convalescent serum samples were collected from 115 client-owned horses in 23 outbreaks of respiratory disease in Ontario. Sera were paired and tested for antibody to equine influenza 1 (AE1-H7N7), equine influenza 2 (AE2-H3N8), equine herpesvirus 1 and 4 (EHV1 and EHV4), and equine rhinitis A and B (ERAV and ERBV). Overall, the cause-specific mor...
Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi.
Pulmonary pharmacology & therapeutics    December 31, 2010   Volume 24, Issue 2 221-226 doi: 10.1016/j.pupt.2010.12.008
Matera MG, Calzetta L, Rogliani P, Bardaro F, Page CP, Cazzola M.Equine obstructive pulmonary disease, also known as heaves or recurrent airway obstruction (RAO) is a common equine pulmonary disease with some similarities to human asthma and COPD, which represents a major cause of morbidity and loss of lung performance. Salbutamol has been widely used for the treatment of human airway diseases and has usually been prepared as the racemic form of the drug. However, recently the R-enantiomer of salbutamol has been introduced into clinical practice in the treatment of asthma in humans and this has been suggested to be an improvement on the racemic form of the ...
Installation of mechanical ventilation in a horse stable: effects on air quality and human and equine airways.
Environmental health and preventive medicine    December 25, 2010   Volume 16, Issue 4 264-272 doi: 10.1007/s12199-010-0195-5
Wålinder R, Riihimäki M, Bohlin S, Hogstedt C, Nordquist T, Raine A, Pringle J, Elfman L.To examine the effects of installing a mechanical ventilation system at a riding-school stable on indoor air quality and human and horse airways. Methods: The intervention was the installation of mechanical ventilation in a riding-school stable. Carbon dioxide (CO2), ammonia, particles, horse allergen, microorganisms and endotoxins were measured in the stable. The stable-workers and riding-students completed a questionnaire and underwent the following tests: analysis of nasal lavage for inflammation biomarkers; levels of exhaled nitrogen oxide (NO); measurements of daily peak-expiratory flow (...
Identification of mixed equine rhinitis B virus infections leading to further insight on the relationship between genotype, serotype and acid stability phenotype.
Virus research    December 24, 2010   Volume 155, Issue 2 506-513 doi: 10.1016/j.virusres.2010.12.007
Horsington JJ, Gilkerson JR, Hartley CA.Equine rhinitis B virus (ERBV) is the single species in the genus Erbovirus, family Picornaviridae. Equine rhinitis B viruses exist in three serotypes and are associated with respiratory disease in horses. Members of the species vary in stability at acid pH. To date there has been discordance in genotype, serotype and acid stability phenotype groupings. To identify capsid regions associated with acid stability, two viruses were serially treated at pH 3.3 to isolate acid-stable mutants. An acid-stable mutant of the prototype acid-labile serotype 1 virus contained a single amino acid change in t...
Association of owner-reported noise with findings during dynamic respiratory endoscopy in Thoroughbred racehorses.
Equine veterinary journal    December 15, 2010   Volume 43, Issue 1 9-17 doi: 10.1111/j.2042-3306.2010.00152.x
Witte SH, Witte TH, Harriss F, Kelly G, Pollock P.To determine the association between owner-reported noise and findings during dynamic respiratory endoscopy (DRE) in a large case series. Objective: The sensitivity of owner-reported noise for dynamic upper respiratory tract obstructions in horses is low, and the specificity is high. Methods: One hundred horses underwent DRE for the investigation of abnormal respiratory noise and/or poor performance. The association of abnormal noise with findings during DRE was evaluated. Results: Eighty-five horses underwent DRE for the investigation of abnormal respiratory noise. Of these, 82% were found to...
Exercising upper respiratory videoendoscopic evaluation of 100 nonracing performance horses with abnormal respiratory noise and/or poor performance.
Equine veterinary journal    December 15, 2010   Volume 43, Issue 1 3-8 doi: 10.1111/j.2042-3306.2010.00132.x
Davidson EJ, Martin BB, Boston RC, Parente EJ.Although well documented in racehorses, there is paucity in the literature regarding the prevalence of dynamic upper airway abnormalities in nonracing performance horses. Objective: To describe upper airway function of nonracing performance horses with abnormal respiratory noise and/or poor performance via exercising upper airway videoendoscopy. Methods: Medical records of nonracing performance horses admitted for exercising evaluation with a chief complaint of abnormal respiratory noise and/or poor performance were reviewed. All horses had video recordings of resting and exercising upper airw...
Pharmacokinetics in pulmonary epithelial lining fluid and plasma of ampicillin and pivampicillin administered to horses.
Research in veterinary science    December 7, 2010   Volume 92, Issue 1 111-115 doi: 10.1016/j.rvsc.2010.11.001
Winther L, Baptiste KE, Friis C.Ampicillin concentrations in pulmonary epithelial lining fluid (PELF) and plasma was studied after single intravenous ampicillin administration (15mg/kg) or single intragastric administration of its prodrug, pivampicillin (19.9mg/kg) to horses and discussed in relation to minimum inhibitory concentrations (MIC) of common equine respiratory pathogens. After intravenous administration, elimination of ampicillin was fast and not detectable in plasma after 12h in three out of six horses. Pivampicillin was absorbed well in non-fasted horses with an oral bioavailability of 36%. The degree of penetra...
Equine influenza virus: a jumping virus that races with Thoroughbred horses and greyhounds.
Veterinary journal (London, England : 1997)    November 30, 2010   Volume 189, Issue 1 3-4 doi: 10.1016/j.tvjl.2010.10.023
Murcia PR, Wood JL.No abstract available
Evaluation of cytokine mRNA expression in bronchoalveolar lavage cells from horses with inflammatory airway disease.
Veterinary immunology and immunopathology    November 30, 2010   Volume 140, Issue 1-2 82-89 doi: 10.1016/j.vetimm.2010.11.018
Hughes KJ, Nicolson L, Da Costa N, Franklin SH, Allen KJ, Dunham SP.Inflammatory airway disease (IAD) is a common disorder of performance horses and is associated with poor performance and accumulation of mucus and inflammatory cells in lower airway secretions. Horses with IAD frequently have increased relative counts of neutrophils in bronchoalveolar lavage fluid (BALF); less commonly relative counts of eosinophils and/or mast cells may be increased. The aetiopathogenesis of IAD is unknown and may involve innate and/or acquired immune responses to various factors including respirable dust constituents, micro-organisms, noxious gases and unconditioned air. The...
IgE, IgGa, IgGb and IgG(T) serum antibody levels in offspring of two sires affected with equine recurrent airway obstruction.
Animal genetics    November 26, 2010   Volume 41 Suppl 2 131-137 doi: 10.1111/j.1365-2052.2010.02122.x
Scharrenberg A, Gerber V, Swinburne JE, Wilson AD, Klukowska-Rötzler J, Laumen E, Marti E.Equine recurrent airway obstruction (RAO) is a chronic lower airway disease of the horse caused by hypersensitivity reactions to inhaled stable dust, including mould spores such as Aspergillus fumigatus. The goals of this study were to investigate whether total serum IgE levels and allergen-specific IgE and IgG subclasses are influenced by genetic factors and/or RAO and whether quantitative trait loci (QTL) could be identified for these parameters. The offspring of two RAO-affected sires (S1: n=56 and S2: n=65) were grouped by stallion and disease status, and total serum IgE levels and specifi...
Exercising videoendoscopic evaluation of 45 horses with respiratory noise and/or poor performance after laryngoplasty.
Veterinary surgery : VS    November 15, 2010   Volume 39, Issue 8 942-948 doi: 10.1111/j.1532-950X.2010.00746.x
Davidson EJ, Martin BB, Rieger RH, Parente EJ.To (1) assess upper airway function by videoendoscopy in horses performing poorly after laryngoplasty and (2) establish whether dynamic collapse of the left arytenoid can be predicted by the degree of resting postsurgical abduction. Methods: Case series. Methods: Horses that had left laryngoplasty (n=45). Methods: Medical records (June 1993-December 2007) of horses evaluated for abnormal respiratory noise and/or poor performance after laryngoplasty were reviewed. Horses with video recordings of resting and exercising upper airway endoscopy were included and postsurgical abduction categorized. ...
Efficacy and safety of sound wave treatment of recurrent airway obstruction in horses.
Journal of veterinary internal medicine    November 9, 2010   Volume 24, Issue 6 1503-1508 doi: 10.1111/j.1939-1676.2010.0634.x
Goncarovs KO, Miskovic Feutz M, Perez-Moreno C, Couetil LL.One proposed nonmedical therapy for recurrent airway obstruction (RAO) in horses is a handheld acoustic device that propels sound waves from the nose down the tracheobronchial tree where it is intended to dislodge mucous and relax bronchospasm, permitting clearance of mucoid secretions. Objective: To evaluate the effectiveness and safety of this device when used as per the manufacturer's recommendations as a treatment for RAO. Methods: Nine adult horses previously diagnosed with RAO. Methods: Prospective, cross-over clinical trial. Horses were exposed to a dusty environment until airway obstru...
Caudal vena cava thrombosis-like syndrome in a horse.
The Canadian veterinary journal = La revue veterinaire canadienne    November 3, 2010   Volume 51, Issue 8 891-894 
Schoster A, Anderson ME.A 9-year-old Quarter horse was presented for chronic refractory pneumonia. On necropsy, an hepatic abscess, caudal vena cava thrombosis, pulmonary thromboembolism, and embolic pneumonia were identified. Similar lesions have been reported in cattle as caudal vena cava thrombosis syndrome, however this syndrome has not previously been reported in horses. Un cheval Quarter horse âgé de 9 ans est présenté pour une pneumonie réfractaire chronique. À la nécropsie, un abcès hépatique, une thrombose de la veine cave caudale, un thromboembolisme pulmonaire et une pneumonie embolique ont été...
Incidence of swallowing during exercise in horses with dorsal displacement of the soft palate.
Equine veterinary journal    November 3, 2010   Volume 42, Issue 8 732-737 doi: 10.1111/j.2042-3306.2010.00116.x
Pigott JH, Ducharme NG, Mitchell LM, Soderholm LV, Cheetham J.The relationship between dorsal displacement of the soft palate (DDSP) and swallowing is unclear. Objective: To quantify the relationship between DDSP and swallowing in horses at exercise. Objective: The frequency of swallowing increases immediately prior to DDSP in horses at exercise. Methods: Videoendoscopic and upper airway pressure data were collated from horses with a definitive diagnosis of DDSP at exercise. Horses with no upper airway abnormalities were matched by age, breed and sex and used as controls. Sixty-nine horses were identified with a definitive diagnosis of DDSP during the st...
Infectivity and pathogenicity of canine H3N8 influenza A virus in horses.
Influenza and other respiratory viruses    October 21, 2010   Volume 4, Issue 6 345-351 doi: 10.1111/j.1750-2659.2010.00157.x
Yamanaka T, Tsujimura K, Kondo T, Matsumura T, Ishida H, Kiso M, Hidari KI, Suzuki T.Equine H3N8 influenza A viruses (EIVs) cause respiratory disease in horses and circulate among horses worldwide. In 2004, an outbreak of canine H3N8 influenza A virus (CIV) occurred among dogs in Florida and has spread among dogs in the United States (US). Genetic analyses revealed that this CIV is closely related to the recent EIVs. Although CIV-infected dogs could be the source of H3N8 influenza A virus for horses, it remains unclear whether the CIV circulating in the United States still maintains its infectivity and/or pathogenicity in horses. To address this, we investigated the infectivit...
Equine influenza – surveillance and control.
Influenza and other respiratory viruses    October 21, 2010   Volume 4, Issue 6 339-344 doi: 10.1111/j.1750-2659.2010.00176.x
Cullinane A, Elton D, Mumford J.Equine influenza virus (EIV) is considered the most important respiratory virus of horses because it is highly contagious and has the potential to disrupt major equestrian events. Equine influenza (EI) can be controlled by vaccination but it has been demonstrated repeatedly in the field that antigenic drift impacts on vaccine efficacy. EI surveillance maintains awareness of emergence and international spread of antigenic variants. It not only serves as an early warning system for horse owners, trainers and veterinary clinicians but is fundamental to influenza control programmes based on vaccin...
Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma.
American journal of respiratory cell and molecular biology    October 8, 2010   Volume 45, Issue 1 181-187 doi: 10.1165/rcmb.2010-0300OC
Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in asthma, but whether it remains a dynamic process late in the course of the disease is unknown. Moreover, little is known about the effects of an antigenic exposure on chronically established smooth muscle remodeling. We measured the effects of antigenic exposure on airway smooth muscle in the central and peripheral airways of horses with heaves, a naturally occurring airway disease that shares similarities with chronic asthma. Heaves-affected horses (n = 6) and age-matched control horses (n = 5) were kept on pastu...
Humoral and cell-mediated immune responses of old horses following recombinant canarypox virus vaccination and subsequent challenge infection.
Veterinary immunology and immunopathology    October 7, 2010   Volume 139, Issue 2-4 128-140 doi: 10.1016/j.vetimm.2010.09.006
Adams AA, Sturgill TL, Breathnach CC, Chambers TM, Siger L, Minke JM, Horohov DW.Equine influenza virus is a leading cause of respiratory disease in the horse population; however, the susceptibility of old horses to EIV infection remains unknown. While advanced age in horses (>20 years) is associated with age-related changes in immune function, there are no specific recommendations regarding the vaccination of older horses even though a well-characterized effect of aging is a reduced antibody response to standard vaccination. Therefore, we evaluated the immunological and physiological response of aged horses to a live non-replicating canarypox-vectored EIV vaccine and s...
Detection of reaginic antibodies against Faenia rectivirgula from the serum of horses affected with Recurrent Airway Obstruction by an in vitro bioassay.
Veterinary research communications    September 3, 2010   Volume 34, Issue 8 719-726 doi: 10.1007/s11259-010-9440-z
Morán G, Folch H, Araya O, Burgos R, Barria M.Reaginic antibodies, mainly of the IgE and some IgG subclasses, play an important role in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. Previously, several studies have investigated the role of reaginic antibodies in the pathogenesis of RAO. However, whereas immunological aspects of RAO have been extensively studied, the precise sequence of events is still not well understood and role of IgE in this disease still remains controversial. Therefo...
Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim.
Journal of veterinary pharmacology and therapeutics    August 24, 2010   Volume 34, Issue 3 277-284 doi: 10.1111/j.1365-2885.2010.01228.x
Winther L, Guardabassi L, Baptiste KE, Friis C.Sulfadiazine (SDZ) and trimethoprim (TMP) concentrations were examined in plasma and pulmonary epithelial lining fluid (PELF), following intravenous and oral administration and compared to minimum inhibitory concentrations (MICs) of common bacterial isolates from equine lower airway infections. SDZ/TMP (25/5 mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24 h, after administration. PELF samples were collected via a tampon device four times after drug administration and analysed for drug concentrations. Add...
Extraluminal, C shaped polyethylene prostheses in two ponies with tracheal collapse.
Veterinary surgery : VS    August 14, 2010   Volume 39, Issue 6 776-783 doi: 10.1111/j.1532-950X.2010.00715.x
Busschers E, Epstein KL, Holt DE, Parente EJ.To describe the surgical technique, complications, and outcome after use of extraluminal prostheses in 2 ponies with severe tracheal collapse. Methods: Clinical report. Methods: Ponies (n=2) with severe tracheal collapse. Methods: A ventral median approach was used to expose the trachea from the larynx to the manubrium. Extraluminal, high-density polyethylene, C-shaped prostheses were sutured to the dorsal tracheal membrane and tracheal rings to provide external tracheal support. Results: The surgical approach provided good tracheal access and placement of the rings was uncomplicated. Initial ...
Clara cell secretory protein increases phagocytic and decreases oxidative activity of neutrophils.
Veterinary immunology and immunopathology    August 6, 2010   Volume 139, Issue 1 1-9 doi: 10.1016/j.vetimm.2010.07.021
Katavolos P, Ackerley CA, Clark ME, Bienzle D.Horses suffer from recurrent airway obstruction, an asthma-like condition induced by repeat inhalation of environmental substances present in barn air. Clara cell secretory protein (CCSP) is much reduced during active inflammation when neutrophils predominate in the airways, and in chronic asthmatics. We sought to investigate morphologic and functional interactions of CCSP with neutrophils. Bronchoalveolar and blood neutrophils from healthy control animals, and from animals with recurrent airway obstruction in remission and exacerbation, were evaluated by immuno-cytochemistry and immuno-electr...
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