Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Exacerbations”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1991

Treatment of acute exacerbations of chronic bronchitis: state of the art.

Effective treatment of acute bacterial exacerbations of chronic bronchitis (ABE) reduces the number of such exacerbations in such patients and may decrease or eliminate background symptoms and improve pulmonary function. The pathologic and physiologic abnormalities of the bronchial system in chronic bronchitis that predispose to bacterial infection probably include impaired mucociliary clearance, obstructed bronchioles, and bacterial infections of the bronchial epithelium. Exacerbations of bronchopulmonary symptoms are usually observed with ABE, although these symptoms are not unique to ABE. While culture and sensitivity testing is not usually required, microscopic examination of sputum is critical to determine the presence of bacterial infection. Bacteria in numbers significantly above the levels present when the patient's condition is stable and at least a doubling of the sputum neutrophil inflammatory level are essential criteria. Bacterial species observed with ABE include Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Neisseria species, with a lesser incidence of Klebsiella and Pseudomonas species. One or more elements of background therapy for ABE should accompany antimicrobial therapy, for example, physiotherapy, bronchodilators, and so forth. Ampicillin is effective, safe, economical, and thus remains the drug of choice for ABE. Quinolones are an effective alternative when ampicillin cannot be tolerated or if organisms are resistant. Dosing is at the upper range of recommendations, and the chosen drug should be given for a 10-14-day regimen. Patients should be reevaluated if symptoms and physical findings do not return to baseline after 5-7 days.

Acute Disease↗
PubMed1992

A double-blind study of two dosage regimens of lomefloxacin in bacteriologically proven exacerbations of chronic bronchitis of gram-negative etiology.

Lomefloxacin has been shown to produce high and sustained concentrations in serum and bronchial mucosa after once-daily administration. This study was designed to assess whether a dose response exists for 400 mg lomefloxacin given once daily or twice daily for 10 days in the treatment of acute bacterial exacerbations of chronic bronchitis of gram-negative etiology. A total of 100 adult patients with acute exacerbations of chronic bronchitis were enrolled at 10 study sites in Germany. Patients with confirmed bacterial pathogens in the baseline sputum culture (once-daily group n = 49, twice-daily group n = 47) were eligible for analysis of bacteriologic and clinical efficacy. The eradication rates for the most frequently isolated baseline pathogens, Haemophilus influenzae, Pseudomonas aeruginosa, and Klebsiella pneumoniae, were at least 75% for both treatment regimens. Overall, once-daily treatment eradicated baseline pathogens in 42 of 49 (85.7%) patients, while twice-daily treatment eradicated pathogens in 43 of 47 (91.5%). This difference was not statistically significant (p = 0.226). Clinically, 47 of 49 (95.9%) patients in the once-daily group and 46 of 47 (97.9%) in the twice-daily group were cured or improved (p = 0.307). Both regimens were well tolerated; there were no differences in the incidence (six patients in each group), types, or severity of adverse events, nor was there clinical evidence of theophylline interaction. The results of this study demonstrate that once-daily treatment with 400 mg lomefloxacin is as effective as twice-daily dosing with 400 mg in patients with acute bacterial exacerbations of chronic bronchitis.

Adult↗
PubMed1992

Safety and efficacy of lomefloxacin versus cefaclor in the treatment of acute exacerbations of chronic bronchitis.

In two multicenter trials, lomefloxacin and cefaclor were compared as treatments for acute bacterial exacerbations of chronic bronchitis. In total, 522 adult outpatients were enrolled at 50 centers in the United States. Patients were randomized to treatment groups receiving either 400 mg lomefloxacin orally once daily (n = 259) or 250 mg cefaclor every 8 hours (n = 263) for 7-10 days. Both groups were comparable in terms of age, severity of exacerbation, smoking history, theophylline use, and baseline pathogens. The most common baseline pathogens were Haemophilus influenzae, found in 32% of patients in the lomefloxacin group and in 29% in the cefaclor group, Pseudomonas aeruginosa (13% and 16%, respectively), Moraxella (Branhamella) catarrhalis (12% and 13%), and Streptococcus pneumoniae (10% in both groups). Bacterial eradication rates 1-4 days after the completion of treatment for all patients with baseline pathogens were 81.8% in the lomefloxacin group and 62.7% in the cefaclor group (p less than 0.001). Clinical success (disappearance or improvement of presenting signs and symptoms) was noted in 80.0% of patients in the lomefloxacin group and 64.7% in the cefaclor group (p = 0.002). Eradication rates for the subgroup of patients who had pathogens susceptible in vitro to both study drugs and who completed treatment were 97.1% for lomefloxacin and 84.6% for cefaclor (p = 0.002). Clinical success rates in this subgroup were 92.4% for lomefloxacin and 90.1 for cefaclor (p = 0.585). Treatment-related adverse events were reported for 7% of patients in the lomefloxacin group and 5% in the cefaclor group. The most common adverse events in both groups were nausea and diarrhea. Six patients were withdrawn from treatment with lomefloxacin and four from the cefaclor group because of adverse events. There was no clinical or laboratory evidence of theophylline interaction with either treatment. Once-daily oral administration of 400 mg lomefloxacin was an effective, well-tolerated alternative to 250 mg of cefaclor three times daily in the treatment of acute exacerbations of chronic bronchitis.

Acute Disease↗
PubMed1995

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Adult↗
PubMed1995

Haloperidol and reduced haloperidol-induced exacerbation of the dystonia produced by the kappa opioid U50,488H in guinea-pigs is associated with inhibition of sigma binding sites: behavioural and autoradiographical studies.

A single dose of haloperidol and reduced haloperidol has been found to exacerbate the dystonic response produced by U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) -cyclohexyl]-benzeacetamide methane sulphonate) in guinea-pigs [8]. The present study sought to correlate the behavioural effect of haloperidol and reduced haloperidol with their effect on inhibition of sigma binding sites in guinea-pig brain using receptor binding and semi-quantitative autoradiography. In the first experiments, groups of guinea-pigs were injected with saline (control, n = 12), haloperidol (0.1 and 1 mg/kg i.p., n = 5) or reduced haloperidol (0.1 and 1 mg/kg i.p., n = 5) 1, 3 and 10 days before, followed by U50,488H (10 mg/kg s.c.) and the effect on the dystonic response rated using a behavioural rating scale [8]. In the second experiments, animals (n = 5) were injected with saline, haloperidol and reduced haloperidol as above and killed 1, 3 and 10 days later, their brains removed, dissected and tissue sections processed for sigma binding site autoradiography using [3H]3-(3-hydroxyphenyl)-N-(n-propyl)piperidine ([3H]-3-PPP). Triplicate tissue sections were wiped using GF/C filters and radioactivity counted. Injection of haloperidol and reduced haloperidol 1, 3 and 10 days earlier exacerbated the dystonic response by decreasing the latency to maximal dystonia and increasing the duration of the response at each dose tested compared with saline-treated animals. These effects of haloperidol and reduced haloperidol on latency and duration were time-related since the effect at 1 > 3 > 10 days. In addition, [3H]-3-PPP binding was inhibited by haloperidol and reduced haloperidol in a dose-and time-related manner. For example, % inhibition of [3H]-3-PPP binding for haloperidol (1 mg/kg) > haloperidol (0.1 mg/kg) and % inhibition of binding (mean +/- SEM) produced by haloperidol (0.1 mg/kg) at 1 (96.1 +/- 2.4) > 3 (74.8 +/- 4.8) > 10 days (36.2 +/- 1.6). Similar results were obtained for haloperidol (1 mg/kg) and reduced haloperidol (0.1 and 1 mg/kg). [3H]-3-PPP autoradiography confirmed these binding data. The results indicate that the exacerbation by sigma ligands of the dystonia produced by U50,488H was associated with the degree of inhibition of [3H]-3-PPP binding.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Serology of acute exacerbation in chronic hepatitis B virus infection.

BACKGROUND: Liver injury in many patients with chronic hepatitis B is sporadic and is often characterized by acute exacerbations alternating with relatively normal liver function. The aim of this study was to perform detailed serological and biochemical analysis during periods of active liver disease to better understand the mechanisms responsible for the cyclic nature of liver injury. METHODS: A series of serum samples from 19 hepatitis B e antigen (HBeAg)-positive patients were analyzed for alterations in serum hepatitis B virus (HBV) DNA, HBeAg, anti-HBe production, and HBeAg-specific immune complex formation before, during, and after spontaneous acute exacerbations of liver injury. RESULTS: This analysis revealed significant correlations between increasing levels of serum HBV DNA, HBeAg, HBeAg-specific immune complexes, and liver injury. These results suggest that increases in viral replication and accumulation of viral proteins in the serum and intracellularly and the subsequent immune response play an important role in initiating acute exacerbations of liver injury in chronic hepatitis B infection. CONCLUSIONS: We propose that production of the secreted and cellular forms of the nucleoprotein reaches a threshold level and elicits specific immune responses, which mediate liver injury.

Antibodies, Monoclonal↗
PubMed1986

Acute pulpal-alveolar cellulitis syndrome. IV. Exacerbations during endodontic treatment: a clinical study of specific microbial isolates and their etiologic role. Part 1.

A statement has been made by Sundqvist that it has not been possible to isolate the specific bacteria that is responsible for acute exacerbations during endodontic treatment of existing periapical inflammation. This clinical study presents specific microbial isolates from 34 intact nonvital teeth involved with acute cellulitis exacerbations during endodontic therapy. No obligate anaerobes were isolated. Forty-seven aerobic and facultative microbes were isolated. Streptococci, primarily facultative, were the major group of microbes isolated (80%); alpha hemolytic streptococci and the group D enterococcus were predominant as mixed and pure culture specimens. Gram-negative microbes as strict aerobic and facultative microbes were also reported as specific isolates. The biological role of anaerobes were discussed in primary pulpal-periapical infections. The alteration of the tissue oxidation-reduction potential, (Eh) is proposed as an etiologic factor in cellulitis exacerbations during endodontic treatment. This is further substantiated in the Part 2 report. Attention is drawn to the pathogenic potential of streptococci and other microbes isolated in this study.

Acute Disease↗
PubMed1989

Cellular and humoral observations in a patient with allergic bronchopulmonary aspergillosis during a nonasthmatic exacerbation.

A patient is described with an asymptomatic exacerbation of allergic bronchopulmonary aspergillosis (ABPA), clinically characterized by pulmonary infiltrates, with absence of obstructive reactions and a short period of hemoptysis 2 weeks before hospitalization. Cell counts and antibody concentrations were measured in serum, and bronchoalveolar fluid (BAF) samples and values were compared with data from previous periods of symptomatic exacerbations. During the asymptomatic exacerbation, concentrations of antibody to Aspergillus fumigatus, total IgE, and precipitating antibodies were elevated in peripheral blood. No quantitative differences in specific antibody concentrations (IgE, IgG, IgA, and IgM) against A. fumigatus were found between sera from symptomatic and asymptomatic periods of ABPA. In contrast to observations in the serum, protein concentrations in BAL fluid were normal during the asymptomatic period, whereas high concentrations were found during the symptomatic phases. Local antibody concentrations (in BAF) were characterized by high levels of IgA antibodies against A. fumigatus. During asymptomatic and symptomatic phases, eosinophils were elevated in peripheral blood, in sputum, in BAF, and highly elevated in tissue biopsy specimens. Activated eosinophils were found, as indicated by the presence of light-density cells in the circulation and monoclonal antieosinophil cationic protein binding to bronchoalveolar lavage eosinophils. In contrast to the symptomatic phase of ABPA in 1980, demonstrating aspecific airway reactivity to several pharmacologically active substances, no such hyperreactivity was found during the asymptomatic phase of ABPA in 1986. It is proposed that the asymptomatic infiltrative phase of ABPA is an intermediate stage that can develop into a symptomatic phase after prolonged and intensified infiltration of eosinophils. Mediators from the inflammatory cells may be involved in the induction of bronchial hyperresponsiveness. After induction of this hyperreactive stage of the airways, additional liberation of mediators from either eosinophils and/or mast cells will lead to a symptomatic (obstructive) phase of ABPA.

Adult↗
PubMed1995

Links between prolonged exposure to xenobiotics, increased incidence of hepatopathies, immunological disturbances and exacerbation of latent Epstein-Barr virus infections.

Disturbances of several humoral and cellular immune parameters are significantly increased in individuals exposed to chemical pollutants. Moreover, exacerbations of the latent Epstein-Barr virus (EBV) infection were more frequently observed in the chemically exposed group than in the control groups. A significant correlation was seen between EBV exacerbations and the increased number of eosinophils, T-lymphocyte rosette formation and the respiratory burst of polymorphonuclear blood cells. Possible links between hepatopathy due to xenobiotics exposition, immunological disturbances and EBV exacerbation are discussed, including a putative role of EBV-induced (autocrine) cytokines.

Antibodies, Viral↗
PubMed1990

Theophylline concentrations in patients with acute exacerbation of COPD.

Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) frequently report a history of theophylline use prior to arrival in the emergency department. The reliability of using this history to guide aminophylline therapy is, however, unclear. The authors studied patients with an acute exacerbation of COPD to determine the relation between the initial theophylline level and the medication history. Seventy-nine patients with a mean age of 64.3 years were entered into the study. The average theophylline level was 10.8 micrograms/mL. Forty-seven percent of the patients had subtherapeutic levels, 46% had therapeutic levels, and 7% had toxic levels. There were weak although statistically significant correlations between the theophylline level and the interval since the last theophylline dose (r = -.40, P less than .001), as well as with the last recorded outpatient theophylline level (r = .45, P less than .001). However, the theophylline level could not be predicted accurately in a number of patients. The authors conclude, because the prediction rule was often inaccurate, aminophylline therapy in patients with acute exacerbation of COPD should be based on direct measurement of the serum theophylline level.

Aged↗
PubMedDate not supplied

Synergy between activated Leishmania major-specific CD4+ T lymphocytes and bone-marrow-derived cells in the exacerbation of murine cutaneous leishmaniasis.

Mechanisms of exacerbation of murine cutaneous leishmaniasis mediated by Leishmania major-specific CD4+ T lymphocytes were studied. Using a limiting dilution assay for the quantification of Leishmania parasites, the infected tissues (footpad) of lethally irradiated mice were found to contain tenfold less parasites at four days of infection than the footpads of infected unirradiated animals. Injection of bone marrow cells depleted of T cells into irradiated mice at the site of infection led to an increase in parasite numbers to levels equivalent to those seen in unirradiated mice. After injection of either L. major-specific CD4+ T cells, previously shown to exacerbate cutaneous leishmaniasis, into the infected footpad or the intravenous (i.v.) injection of bone marrow cells depleted of T cells, the numbers of parasites in lesions of irradiated mice never reached the values found in unirradiated control mice. In contrast, the concomitant transfer of CD4+ T-cell populations in situ and bone marrow cells depleted of T cells intravenously led to an increase in parasite loads in irradiated mice up to levels comparable to those of the unirradiated mice. This suggested that recruitment of myelomonocytic cells at the site of the lesions plays a role in the exacerbation of murine cutaneous leishmaniasis mediated by these CD4+ T lymphocytes. Finally, a similar effect was observed with T cells specific for an antigen unrelated to Leishmania, provided that this antigen was added to the L. major infecting inoculum.

Animals↗
PubMed2004

Pharmacologic therapy for acute exacerbations of chronic obstructive pulmonary disease: a review.

This article reviews available data on the drug therapy armamentarium for the acute exacerbation of chronic obstructive pulmonary disease (COPD). Summaries of studies and therapeutic issues for bronchodilators, antibiotic therapy, corticosteroid use, and a few miscellaneous agents are presented. Many controversies exist in the criteria defining the acute exacerbation, in defining appropriate outcome parameters for assessment, and, consequently, in developing specific consistent recommendations for drug therapy. Five published guidelines assist the clinician in therapeutic drug management of the acute exacerbation of COPD, and each differs in its recommendations for drug therapy prescription. The article includes synopses for drug therapy recommendations from the guidelines.

Acute Disease↗
PubMed2004

Nutritional support in patients with chronic obstructive pulmonary disease during hospitalization for an acute exacerbation; a randomized controlled feasibility trial.

BACKGROUND & AIMS: Previous studies reported a severely impaired energy balance in COPD patients during the first days of an acute exacerbation, mainly due to a decreased energy and protein intake. The aim of the study was to investigate the feasibility and effectiveness of energy- and protein-rich nutritional supplements during hospitalization for an acute exacerbation in nutritionally depleted COPD patients. METHODS: In a randomized double-blind, placebo-controlled two-center trial, 56 COPD patients were randomized and 47 patients completed the study. Nutritional intervention consisted of 3 x 125 ml (2.38 MJ/day) and the placebo group received similar amounts of a non-caloric fluid. Medical therapy and dietetic consultation were standardized and dietary intake was measured daily. Body composition, respiratory and skeletal muscle strength, lung function and symptoms were measured on admission and on days 4 and 8 of hospitalization. RESULTS: Forty-seven percent of the patients had experienced recent involuntary weight loss prior to admission. The degree of weight loss was inversely related to resting arterial oxygen tension (r = 0.31; P < 0.05). Nutritional intervention resulted in a significant increase in energy (16% vs. placebo) and protein intake (38% vs. placebo). Mean duration of hospitalization was 9 +/- 2 days. Relative to usual care, no additional improvements in lung function or muscle strength were seen after nutritional intervention. CONCLUSIONS: Oral nutritional supplementation during hospitalization for an acute exacerbation is feasible in nutritionally depleted COPD patients and does not interfere with normal dietary intake.

Aged↗
PubMed2006

Evaluation of glycosaminoglycans content and 5-hydroxytryptamine 2B receptor in the heart valves of Sprague-Dawley rats with spontaneous mitral valvulopathy--a possible exacerbation by dl-amphetamine sulfate in Fischer 344 rats?

Spontaneous valvulopathy has been described as nodular or segmental thickenings composed of fibromyxoid tissue in the subendocardium of various valve-leaflets in aging rats, but its pathogenesis and significance are incompletely understood. In this study, we examined the 5-hydroxytryptamine 2B receptor (5HT2BR) expression and characterization of extracellular matrix (ECM) components, and related these to the presence of valvulopathy in the mitral valve-leaflet (spontaneous mitral valvulopathy, SMV) of Sprague-Dawley (SD) rats. We also examined hearts from Fischer 344 (F344) rats treated with dl-amphetamine sulfate for 103 weeks to further explore the potential for drug-induced exacerbation of SMV. In SD rats, valve-leaflets with SMV exhibited a greater valve thickness, a higher amount of glycosaminoglycans, a lower amount of collagen and increased number of 5HT2BR-positive cells. Our data on morphology and ECM changes showed a striking similarity between SMV in SD rats and anorexigen-associated valvulopathy in humans, and increased 5HT2BR-positive cells in SMV implies that 5HT2BR may play a role in pathogenesis. Further, increased incidence and severity of SMV in F344 rats by treatment with dl-amphetamine suggest that a drug-induced exacerbation of SMV may exist in rats. However, additional research is needed to confirm a role for 5HT2BR in the pathogenesis of SMV in SD rats, and to further characterize the relationship between dl-amphetamine treatment and exacerbation of SMV in F344 rats.

Aging↗
PubMedDate not supplied

A cognitive therapy conceptualization of panic disorder exacerbated by interferon treatment.

This case conference presents a patient with von Willebrand disease, receiving year-long interferon treatment for hepatitis C. She was referred to C-L Psychiatry following a severe exacerbation of panic disorder. Our guest interviewer is Dr. Craig White, a Scottish cognitive therapist. The subsequent discussion outlines the treatment challenges of panic disorder that occurs when a patient is receiving interferon. A literature review evaluates psychological effects of interferon and biological mechanisms by which interferon may exacerbate anxiety and depression. A cognitive therapy conceptualization of interferon-induced exacerbation of panic disorder is proposed.

Adult↗
PubMed2004

Acute exacerbations of chronic bronchitis: new developments concerning microbiology and pathophysiology--impact on approaches to risk stratification and therapy.

Exacerbations are a characteristic feature of chronic obstructive pulmonary disease and contribute significantly to associated morbidity and mortality. Renewed interest in this common clinical problem and research using new investigative tools has enhanced substantially the understanding of the pathogenesis of exacerbations. Results of recent clinical trials and observational studies have allowed refinements in treatment of exacerbations that should im-prove patient outcomes. This article discusses a rational, stratified approach to the use of antibiotics for this condition based on these recent studies.

Acute Disease↗
PubMed2005

Whole-cell pertussis vaccine protects against Bordetella pertussis exacerbation of allergic asthma.

The prevalence of asthma and allergic disease has increased in many countries and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether whole-cell pertussis vaccine (Pw) enhanced or prevented B. pertussis induced exacerbation of allergic asthma. Groups of mice were immunized with Pw, infected with B. pertussis and/or sensitized to ovalbumin. Immunological, pathological and physiological changes were measured to assess the impact of Pw immunization on immune deviation and airway function. Pw immunization modulated ovalbumin-specific serum IgE production, and reduced local and systemic IL-13 and other cytokine responses to sensitizing allergen. Histopathological examination revealed Pw immunization reduced the severity of airway pathology and decreased bronchial hyperreactivity to methacholine exposure. Pw does not enhance airway IL-13 and consequently does not enhance but protects against the exacerbation of allergic responses. We find no evidence of Pw contributing to allergic asthma, but rather provide evidence of a mechanism whereby whole-cell pertussis vaccination has a protective role.

Animals↗
PubMed2004

IL-4-independent pathways exacerbate methacholine-induced airway hyperreactivity during mycoplasma respiratory disease.

BACKGROUND: Mycoplasma respiratory infections are associated with wheezing and exacerbation of airway hyperresponsiveness (AHR) in asthmatic patients. IL-4 is a key cytokine in the development of AHR and airway reconstruction in asthmatic patients and might be an important component in exacerbation of AHR during pulmonary mycoplasma infection. OBJECTIVE: This study evaluates the effect of IL-4 on the severity of methacholine-induced AHR associated with mycoplasma pulmonary mycoplasma infection. METHODS: BALB/c and IL-4 knockout (KO) mice were infected with Mycoplasma pulmonis, and their enhanced pause scores were monitored before and after methacholine inhalation with whole-body plethysmography. RESULTS: IL-4 KO mice showed no difference in histopathology of the lungs before or after Mycoplasma pulmonis infection when compared with BALB/c mice. There was an increase in airway obstruction from days 7 to 21 after infection in both strains of mice, but there was no strain difference in airway resistance-associated mycoplasma disease. However, IL-4 KO mice had significantly higher methacholine-induced AHR after M pulmonis infection when compared with BALB/c mice. There was no difference in AHR between uninfected IL-4 KO and control mice. CONCLUSION: In contrast to our hypothesis, IL-4-independent pathways exacerbate methacholine-induced AHR and promote airway obstruction during the pathogenesis of mycoplasma respiratory disease.

Animals↗