RESUMO
In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O3) or HDMA/ozone (HDMA+O3) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA+O3 alters the development process in the lung alveoli.
Assuntos
Poluentes Atmosféricos/toxicidade , Alérgenos/toxicidade , Pulmão/efeitos dos fármacos , Oxidantes/toxicidade , Ozônio/toxicidade , Pyroglyphidae/imunologia , Animais , Animais Recém-Nascidos , Pulmão/anatomia & histologia , Pulmão/crescimento & desenvolvimento , Macaca mulatta , MasculinoRESUMO
BACKGROUND: The risks for infants and young children receiving inhaled corticosteroid (ICS) therapy are largely unknown. Recent clinical studies indicate that ICS therapy in pre-school children with symptoms of asthma result in decreased symptoms without influencing the clinical disease course, but potentially affect postnatal growth and development. The current study employs a primate experimental model to identify the risks posed by ICS therapy. OBJECTIVE: To (1) establish whether ICS therapy in developing primate lungs reverses pulmonary pathobiology associated with allergic airway disease (AAD) and (2) define the impact of ICS on postnatal lung growth and development in primates. METHODS: Infant rhesus monkeys were exposed, from 1 through 6 months, to filtered air (FA) with house dust mite allergen and ozone using a protocol that produces AAD (AAD monkeys), or to FA alone (Control monkeys). From three through 6 months, the monkeys were treated daily with ICS (budesonide) or saline. RESULTS: Several AAD manifestations (airflow restrictions, lavage eosinophilia, basement membrane zone thickening, epithelial mucin composition) were reduced with ICS treatment, without adverse effects on body growth or adrenal function; however, airway branching abnormalities and intraepithelial innervation were not reduced. In addition, several indicators of postnatal lung growth and differentiation: vital capacity, inspiratory capacity, compliance, non-parenchymal lung volume and alveolarization, were increased in both AAD and Control monkeys that received ICS treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Incomplete prevention of pathobiological changes in the airways and disruption of postnatal growth and differentiation of airways and lung parenchyma in response to ICS pose risks for developing primate lungs. These responses also represent two mechanisms that could compromise ICS therapy's ability to alter clinical disease course in young children.
Assuntos
Corticosteroides/farmacologia , Alérgenos/toxicidade , Antígenos de Dermatophagoides/toxicidade , Asma , Pulmão , Animais , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/patologia , Asma/fisiopatologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Pulmão/crescimento & desenvolvimento , Pulmão/patologia , Pulmão/fisiopatologia , Macaca mulatta , MasculinoRESUMO
Pulmonary function hyperresponsiveness, defined as enhanced response on reexposure to O3, compared with initial O3 exposure, has been previously noted in consecutive day exposures to high ambient O3 concentrations (i.e., 0.32-0.42 ppm). Effects of consecutive-day exposure to lower O3 concentrations (0.20-0.25 ppm) have yielded equivocal results. To examine the occurrence of hyperresponsiveness at two levels of O3 exposure, 15 aerobically trained males completed seven 1-h exposures of continuous exercise at work rates eliciting a mean minute ventilation of 60 1/min. Three sets of consecutive-day exposures, involving day 1/day 2 exposures to 0.20/0.20 ppm O3, 0.35/0.20 ppm O3, and 0.35/0.35 ppm O3, were randomly delivered via an obligatory mouthpiece inhalation system. A filtered-air exposure was randomly placed 24 h before one of the three sets. Treatment effects were assessed by standard pulmonary function tests, exercise ventilatory pattern (i.e., respiratory frequency, f; and tidal volume, VT) changes and subjective symptom (SS) response. Initial O3 exposures to 0.35 and 0.20 ppm had a statistically significant effect, compared with filtered air, on all measurements. On reexposure to 0.35 ppm O3 24 h after an initial 0.35 ppm O3 exposure, significant hyperresponsiveness was demonstrated for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), f, VT, and total SS score. Exposure to 0.20 ppm O3 24 h after 0.35 ppm O3 exposure, however, resulted in significantly enhanced responses (compared with initial 0.20 ppm O3 exposure) only for FEV1, f, and VT.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Pulmão/efeitos dos fármacos , Ozônio/farmacologia , Respiração/efeitos dos fármacos , Adulto , Fluxo Expiratório Forçado , Volume Expiratório Forçado , Humanos , Pulmão/fisiologia , Masculino , Consumo de Oxigênio , Ozônio/administração & dosagem , Capacidade VitalRESUMO
Previous studies of 2 h of exposure to NO2 at high urban atmospheric levels (i.e., 0.50-1.0 ppm), utilizing light-to-moderate exercise for up to 1 h have failed to demonstrate significant pulmonary dysfunction in healthy humans. To test the hypothesis that heavy sustained exercise would elicit pulmonary dysfunction on exposure to 0.60 ppm NO2 and/or enhance the effects of exposure to 0.30 ppm O3, 40 aerobically trained young adults (20 males and 20 females) completed 1 h of continuous exercise at work rates eliciting a mean minute ventilation of 70 and 50 l/min for the males and females, respectively. Exposures to filtered air, 0.60 ppm NO2, 0.30 ppm O3, and 0.60 ppm NO2 plus 0.30 ppm O3 were randomly delivered via an obligatory mouthpiece inhalation system. Treatment effects were assessed by standard pulmonary function tests and exercise ventilatory and subjective symptoms response. Two-way analysis of variance with repeated measures and post hoc analyses revealed a statistically significant (P less than 0.05) effect of O3 on forced expiratory parameters, specific airway resistance, exercise ventilatory response, and reported subjective symptoms of respiratory discomfort. In contrast, no significant effect of NO2 was observed nor was there any significant interaction of NO2 and O3 in combination. There were no significant differences between male and female responses to gas mixture treatments. It was concluded that inhalation of 0.60 ppm NO2 for 1 h while engaged in heavy sustained exercise does not elicit effects evidenced by measurement techniques used in this study nor evoke additive effects beyond those induced by 0.30 ppm O3 in healthy young adults.
Assuntos
Óxido Nitroso/farmacologia , Ozônio/farmacologia , Adulto , Combinação de Medicamentos , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , Testes de Função Respiratória , AutoimagemRESUMO
In 19 dogs anesthetized with xylazine and alpha-chloralose, we examined the influence of background vagal C-fiber activity on the breathing pattern using a modified perineural capsaicin treatment. In seven dogs, we tested the efficacy of this treatment by recording compound action potentials before and after capsaicin application. In the remaining 12 dogs, we examined the effect of vagal perineural capsaicin on the Hering-Breuer expiratory facilitatory inflation reflex, pulmonary chemoreflex, and breathing pattern (tidal volume and expiratory and inspiratory times). Neither the peak height nor integral of the A wave of the compound action potential was significantly affected. However, the peak height and integral of the C wave of the compound action potential were significantly affected. However, the peak height and integral of the C wave of the compound action potential were significantly reduced. The myelinated fiber-initiated Hering-Breuer reflex remained intact after perineural capsaicin, but the C-fiber-initiated pulmonary chemoreflex was abolished. Perineural capsaicin increased tidal volume (0.399 +/- 0.031 to 0.498 +/- 0.058 liter; P < 0.05), expiratory time (3.62 +/- 0.31 to 4.82 +/- 0.68 s; P < 0.05), inspiratory time (1.49 +/- 0.12 to 1.72 +/- 0.17 s; P < 0.10) and total time per breath (5.11 +/- 1.08 to 6.54 +/- 0.82 s; P < 0.05). We conclude that background vagal C-fiber activity exerts an inhibitory effect on tidal volume and an excitatory effect on breathing frequency.
Assuntos
Fibras Nervosas/fisiologia , Mecânica Respiratória/fisiologia , Nervo Vago/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Anestesia , Animais , Gasometria , Capsaicina/farmacologia , Cães , Hemodinâmica/efeitos dos fármacos , Fibras Nervosas/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Mecânica Respiratória/efeitos dos fármacos , Estimulação Química , Nervo Vago/citologia , Nervo Vago/efeitos dos fármacosRESUMO
We examined the contribution of afferent vagal A- and C-fibers on abdominal expiratory muscle activity (EMA). In seven spontaneously breathing supine dogs anesthetized with alpha-chloralose we recorded the electromyogram of the external oblique muscle at various vagal temperatures before and after the induction of a pneumothorax. When myelinated fibers were blocked selectively by cooling the vagus nerves to 7 degrees C, EMA decreased to 40% of control (EMA at 39 degrees C). With further cooling to 0 degrees C, removing afferent vagal C-fiber activity, EMA returned to 72% of control. On rewarming the vagus nerves to 39 degrees C, we then induced a pneumothorax (27 ml/kg) that eliminated the EMA in all the dogs studied. Cooling the vagus nerves to 7 degrees C, during the pneumothorax, produced a slight though not significant increase in EMA. However, further cooling of the vagus nerves to 0 degrees C caused the EMA to return vigorously to 116% of control. In three dogs, intravenous infusion of a constant incrementally increasing dose of capsaicin, a C-fiber stimulant, decreased EMA in proportion to the dose delivered. These results suggest that EMA is modulated by a balance between excitatory vagal A-fiber activity, most likely from slowly adapting pulmonary stretch receptors, and inhibitory C-fiber activity, most likely from lung C-fibers.
Assuntos
Músculos Respiratórios/inervação , Nervo Vago/fisiologia , Abdome , Vias Aferentes/fisiologia , Animais , Capsaicina/farmacologia , Temperatura Baixa , Cães , Eletromiografia , Fibras Nervosas/fisiologia , Pneumotórax/fisiopatologia , Reflexo/fisiologia , Músculos Respiratórios/efeitos dos fármacos , Músculos Respiratórios/fisiologiaRESUMO
Acute inhalation of ozone induces vagally mediated rapid shallow breathing and bronchoconstriction. In spontaneously breathing anesthetized dogs, we attempted to determine whether afferent vagal C-fibers in the lower airways contributed to these responses. Dogs inhaled 3 ppm ozone for 40-70 min into the lower trachea while cervical vagal temperature was maintained successively at 37, 7, and 0 degrees C. At 37 degrees C, addition of ozone to the inspired air decreased tidal volume and dynamic lung compliance and increased breathing frequency, total lung resistance, and tracheal smooth muscle tension. Ozone still evoked significant effects when conduction in myelinated vagal axons was blocked selectively by cooling the nerves to 7 degrees C. Ozone-induced effects were largely abolished when nonmyelinated vagal axons were blocked by cooling to 0 degree C, breathing during ozone inhalation at 0 degree C being generally similar to that during air breathing at 0 degree C, except that minute volume and inspiratory flow were higher. We conclude that afferent vagal C-fibers in the lower airways make a major contribution to the acute respiratory effects of ozone and that nonvagal afferents contribute to the effects that survive vagal blockade.
Assuntos
Neurônios Aferentes/fisiologia , Ozônio/farmacologia , Reflexo/fisiologia , Respiração/fisiologia , Nervo Vago/fisiologia , Administração por Inalação , Animais , Pressão Sanguínea/efeitos dos fármacos , Broncoconstrição/efeitos dos fármacos , Temperatura Baixa , Cães , Contração Isométrica/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/fisiologia , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/fisiologia , Ozônio/administração & dosagem , Reflexo/efeitos dos fármacos , Respiração/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Traqueia/inervação , Nervo Vago/citologiaRESUMO
To identify the afferents responsible for initiating the vagally mediated respiratory changes evoked by acute exposure to ozone, we recorded vagal impulses in anesthetized, open-chest, artificially ventilated dogs and examined the pulmonary afferent response to ozone (2-3 ppm in air) delivered to the lower trachea for 20-60 min. Bronchial C-fibers (BrCs) were the lung afferents most susceptible to ozone, the activity of 10 of 11 BrCs increasing from 0.2 +/- 0.2 to 4.6 +/- 1.3 impulses/s within 1-7 min of ozone exposure. Ten of 15 rapidly adapting receptors (RARs) were stimulated by ozone, their activity increasing from 1.5 +/- 0.4 to 4.7 +/- 0.7 impulses/s. Stimulation of RARs (but not of BrCs) appeared secondary to the ozone-induced reduction of lung compliance because it was abolished by hyperinflation of the lungs. Ozone had little effect on pulmonary C-fibers or slowly adapting pulmonary stretch receptors. Our results suggest that both BrCs and RARs contribute to the tachypnea and bronchoconstriction evoked by acute exposure to ozone when vagal conduction is intact and that BrCs alone are responsible for the vagally mediated tachypnea that survives vagal cooling to 7 degrees C.
Assuntos
Brônquios/inervação , Mecanorreceptores/efeitos dos fármacos , Fibras Nervosas/efeitos dos fármacos , Ozônio/farmacologia , Potenciais de Ação/efeitos dos fármacos , Administração por Inalação , Animais , Cães , Pulmão/inervação , Neurônios Aferentes/efeitos dos fármacos , Ozônio/administração & dosagem , Receptores Pulmonares de Alongamento/efeitos dos fármacos , Respiração Artificial , Mecânica Respiratória/efeitos dos fármacos , Estimulação Química , Volume de Ventilação Pulmonar/efeitos dos fármacos , Nervo Vago/citologia , Nervo Vago/fisiologiaRESUMO
We examined the relationship between C-fiber-mediated, ozone-induced rapid shallow breathing and airway epithelial cell injury at different airway sites within the lower respiratory tract of conscious Wistar rats (n = 24). We combined an acute 8-h ozone inhalation with vagal perineural capsaicin treatment, a selective C-fiber conduction block, and 5-bromo-2'-deoxyuridine (BrdU) labeling as an index of epithelial injury. Vehicle-treated rats that inhaled ozone developed a rapid shallow breathing pattern during ozone inhalation, whereas the capsaicin-treated rats that inhaled ozone showed no changes in respiratory frequency. In vehicle-treated, ozone-exposed rats that developed rapid shallow breathing, a progressive increase in BrdU-labeling density (no. of BrdU-labeled cells/mm(2) airway) was observed starting at the bifurcation of the left main stem bronchi (central airway) and going down either a short or long airway path. In vehicle-treated, ozone-exposed rats, terminal bronchioles supplied by short and long airway paths had a similar degree of BrdU-labeling density that was significantly (P < 0.05) greater than the BrdU-labeling density of the proximal airways that supply them. In contrast, the attenuation of rapid shallow breathing produced by capsaicin treatment resulted in a significantly reduced BrdU-labeling density in the terminal bronchioles supplied by short airway paths compared with the terminal bronchioles supplied by long airway paths. Our data indicate that ozone-induced rapid shallow breathing protects large conducting airways while producing a more even distribution of injury to terminal bronchioles.
Assuntos
Fibras Nervosas/fisiologia , Oxidantes Fotoquímicos/toxicidade , Ozônio/toxicidade , Mecânica Respiratória/efeitos dos fármacos , Animais , Antimetabólitos , Câmaras de Exposição Atmosférica , Bromodesoxiuridina , Contagem de Células , Divisão Celular/fisiologia , Células Epiteliais/patologia , Epitélio/patologia , Ratos , Ratos WistarRESUMO
To assess the role of lung sensory C fibers during and after inhalation of 1 part/million ozone for 8 h, we compared breathing pattern responses and epithelial injury-inflammation-repair in rats depleted of C fibers by systemic administration of capsaicin as neonates and in vehicle-treated control animals. Capsaicin-treated rats did not develop ozone-induced rapid, shallow breathing. Capsaicin-treated rats showed more severe necrosis in the nasal cavity and greater inflammation throughout the respiratory tract than did control rats exposed to ozone. Incorporation of 5-bromo-2'-deoxyuridine (a marker of DNA synthesis associated with proliferation) into terminal bronchiolar epithelial cells was not significantly affected by capsaicin treatment in rats exposed to ozone. However, when normalized to the degree of epithelial necrosis present in each rat studied, there was less 5-bromo-2'-deoxyuridine labeling in the terminal bronchioles of capsaicin-treated rats. These observations suggest that the ozone-induced release of neuropeptides does not measurably contribute to airway inflammation but may play a role in modulating basal and reparative airway epithelial cell proliferation.
Assuntos
Capsaicina/farmacologia , Fibras Nervosas/efeitos dos fármacos , Oxidantes Fotoquímicos/toxicidade , Ozônio/toxicidade , Administração por Inalação , Animais , Antimetabólitos , Bromodesoxiuridina , Epitélio/patologia , Feminino , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Cavidade Nasal/patologia , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Gravidez , Ratos , Ratos Wistar , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , Substância P/metabolismo , Volume de Ventilação Pulmonar/fisiologia , Traqueia/metabolismoRESUMO
Ten highly trained endurance athletes were studied to determine the effects of exposure to low ozone (O3) concentrations on simulated competitive endurance performance and associated physiological and subjective symptom responses. Each subject was randomly exposed to filtered air (FA), and to 0.12, 0.18, and 0.24 ppm O3 while performing a 1 h competitive simulation protocol on a bicycle ergometer. Endurance performance was evaluated by the number of subjects unable to complete rides (last 30 min at an intense work load of approximately 86% VO2max). All subjects completed the FA exposure, whereas one, five, and seven subjects did not complete the 0.12, 0.18, and 0.24 ppm O3 exposures, respectively. Statistical analysis indicated a significant (P less than 0.05) increase in the inability of subjects to complete the competitive simulations with increasing O3 concentration, including a significant difference between the 0.24 ppm O3 and FA exposure. Significant decreases (P less than 0.05) were also observed following the 0.18 and 0.24 ppm O3 exposures, respectively, in forced vital capacity (-7.8 and -9.9%), and forced expiratory volume in 1 s (-5.8 and -10.5%). No significant O3 effect was observed for exercise respiratory metabolism or ventilatory pattern responses. However, the number of reported subjective symptoms increased significantly following the 0.18 and 0.24 ppm O3 protocols. These data demonstrate significant decrements in simulated competitive endurance performance and in pulmonary function, with accompanying enhanced subjective symptoms, following exposure to low O3 levels commonly observed in numerous metropolitan environments during the summer months.
Assuntos
Ozônio/toxicidade , Esforço Físico , Respiração/efeitos dos fármacos , Adulto , Teste de Esforço , Humanos , Medidas de Volume Pulmonar , Resistência Física/efeitos dos fármacos , Fatores de TempoRESUMO
PURPOSE: The purpose of this study was to examine the role of airway receptors in respiratory-related sensations after ascent to altitude. METHODS: Ratings of respiratory-related sensations, perceived exertion and acute mountain sickness, heart rate, and peripheral oxygen saturation were recorded at rest and exercise in male and female subjects who had inhaled either aerosolized saline or saline with tetracaine after acute ascent to an altitude of 3500 m and after prolonged acclimatization of 18 d at altitudes between 4000 and 5000 m. RESULTS: Tetracaine had no effect on respiratory-related sensations at altitude either at rest or during exercise, and male and female subjects experienced similar respiratory-related sensations. Sensations of rapid breathing were experienced at rest after acute exposure to 3500 m as compared with sea level, but not after acclimatization to 5000 m. Sensations of rapid breathing, air hunger, and heavy breathing were experienced during exercise after acute and prolonged altitude exposure as compared with sea level, with a sensation of chest tightness experienced at 3500 m and a sensation of gasping experienced at 5000 m. CONCLUSION: These results suggest that airway afferents play no role in the respiratory-related sensations experienced by male and female subjects either during acute ascent to altitude or after prolonged acclimatization at altitude.
Assuntos
Doença da Altitude/fisiopatologia , Dispneia/fisiopatologia , Fenômenos Fisiológicos Respiratórios , Sistema Respiratório/inervação , Adulto , Dispneia/etiologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Oxigênio/sangue , Percepção , Fatores Sexuais , Tetracaína/farmacologiaRESUMO
Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.
Assuntos
Alérgenos/imunologia , Asma/veterinária , Doenças do Gato/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Animais , Asma/imunologia , Hiper-Reatividade Brônquica , Testes de Provocação Brônquica/veterinária , Líquido da Lavagem Broncoalveolar/imunologia , Gatos , Cynodon/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Cloreto de Metacolina/imunologia , Testes de Função Respiratória/veterináriaRESUMO
Serum samples from six cats with experimentally induced asthma were used to purify feline IgE using gel filtration and affinity chromatography. The resultant IgE, evaluated for purity by immunoelectrophoresis (IEP) and reactivity by Prausnitz-Kustner (PK) testing, was used to develop polyclonal rabbit anti-feline IgE antisera. Using reverse cutaneous anaphylaxis (RCA), the antisera were determined to be specific for feline IgE. The polyclonal rabbit anti-feline IgE antiserum was then validated in an allergen-specific ELISA. Serum samples from an additional five asthmatic cats sensitized with Bermuda grass allergen (BGA) were evaluated prior to sensitization, after parenteral sensitization, and after aerosol sensitization and challenge. A significant increase in serum BGA-specific IgE was noted over time.
Assuntos
Asma/veterinária , Doenças do Gato/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Imunoglobulina E/imunologia , Alérgenos/imunologia , Animais , Anticorpos Anti-Idiotípicos/biossíntese , Asma/sangue , Asma/imunologia , Gatos , Cromatografia em Gel/veterinária , Cynodon/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Soros Imunes/imunologia , Imunoeletroforese/veterinária , Imunoglobulina E/sangue , Imunoglobulina E/isolamento & purificaçãoRESUMO
OBJECTIVE: To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. ANIMALS: 25 male Holstein calves, 8 to 16 weeks old. PROCEDURE: 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. RESULTS: Cumulative incidence of cough, harsh lung sounds, adventitious sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying degrees of necrotizing and proliferative bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. CONCLUSION AND CLINICAL RELEVANCE: Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.
Assuntos
Doenças dos Bovinos/fisiopatologia , Infecções por Vírus Respiratório Sincicial/veterinária , Vírus Sincicial Respiratório Bovino/patogenicidade , Aerossóis , Animais , Gasometria/veterinária , Líquido da Lavagem Broncoalveolar , Bovinos , Doenças dos Bovinos/virologia , Tosse/veterinária , Tosse/virologia , Masculino , Líquido da Lavagem Nasal/virologia , Testes de Função Respiratória/veterinária , Infecções por Vírus Respiratório Sincicial/fisiopatologiaRESUMO
It has been repeatedly observed that ozone (O3) re-exposure within 24 h elicits enhanced pulmonary function responses. However, there are only limited observations concerning re-exposure to O3 at intervals between 24 h and several days. The present study was designed to assess the effects of re-exposure to 0.35 ppm O3 at intervals of 24, 48, 72, and 120 h. Forty young adult male subjects were assigned randomly to one of four groups in ascending order of time to re-exposure (groups 1-4). Each exercised on a bicycle ergometer for 60 min at a workload that elicited a mean ventilation of 60 l/min on three occasions: protocol 1 (P1), filtered air (FA); protocol 2 (P2), 0.35 ppm O3; and protocol 3 (P3), 0.35 ppm O3. In addition to standard pulmonary function measures, specific airway resistance (SRaw); exercise ventilatory pattern, i.e., respiratory frequency (fR) and tidal volume (VT); and subjective symptoms (SS) were assessed. Statistical analysis revealed significant differences (p less than .05) for all groups between the FA (P1) responses and those for the two O3 exposures (P2, P3) for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), SRaw, fR, VT, and SS. When the two O3 exposures (P2 and P3) were compared, only group 1 (24 h) responses were statistically significant upon re-exposure: FEV1.0, -16.1 vs. -30.4% (p less than .003); SRaw, 20.5 vs. 34.5% (p less than .05); fR, 44.2 vs. 65.3% (p less than .001); and SS (p less than .015).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Adaptação Fisiológica , Poluentes Atmosféricos , Pulmão/efeitos dos fármacos , Ozônio/farmacologia , Adulto , Resistência das Vias Respiratórias/efeitos dos fármacos , Exercício Físico , Fluxo Expiratório Forçado , Volume Expiratório Forçado , Humanos , Pulmão/metabolismo , Pulmão/fisiologia , Masculino , Consumo de Oxigênio , Pletismografia Total , Distribuição Aleatória , Fatores de Tempo , Capacidade VitalRESUMO
Breathing route has a profound effect on sulfur dioxide-induced pulmonary function response in human subjects. There is comparatively little evidence of the effects of oral, nasal, and oronasal breathing on ozone (O3)-induced responses in humans. In this study, six young adult males were exposed on five occasions to 0.40 parts per million (ppm) O3 while exercising continuously at one of two workloads (minute ventilation, VE, of approximately 30 and 75 l/min). The VE exposure time product was similar for all protocols. Four exposures were delivered randomly with a Hans-Rudolph respiratory valve attached to a silicone facemask, with breathing route effected with and without noseclip. A 2 x 2 analysis of variance revealed no statistically significant differences (p less than .05) across conditions in pulmonary function, exercise ventilatory pattern, or subjective symptoms responses. The fifth exposure, delivered via the same respiratory valve with mouthpiece, but without facemask, revealed significantly greater forced expiratory volume in 1 s (FEV1.0) impairment than that observed for the respiratory valve, facemask with noseclip exposure (-20.4% and -15.9%, respectively). The latter suggests partial O3 reactivity to the facemask and clean shaven facial surface of the subjects, although reduced oral scrubbing by mouthpiece-induced bypassing of the oral vestibule might account, in part, for this difference. Recent O3 uptake evidence from another laboratory, however, supports our conclusion that breathing route during moderate and heavy continuous exercise does not affect acute physiologic responses to 0.40 ppm O3.
Assuntos
Exercício Físico , Ozônio/farmacologia , Respiração/efeitos dos fármacos , Adulto , Análise de Variância , Volume Expiratório Forçado , Humanos , Masculino , Boca , Nariz , Ozônio/administração & dosagem , Reprodutibilidade dos Testes , Capacidade VitalRESUMO
The acute effect of vagal perineural capsaicin treatment (VPCT) on parasympathetic bradycardia and tracheal neurogenic protein extravasation was examined. In nine anesthetized male Wistar rats the effect of VPCT on the bradycardia induced by electrical stimulation of the vagus was examined. In 24 anesthetized male Wistar rats the effect of VPCT on the tracheal protein extravasation induced by the inhalation of capsaicin aerosols was also studied. VPCT did not alter the bradycardia induced by vagal stimulation or the tracheal protein extravasation induced by the inhalation of capsaicin aerosol. The results of these studies further demonstrate the selectivity of perineural capsaicin treatment on vagal sensory nonmyelinated fibers in the rat and indicate that it is a useful tool for examining the role of sensory vagal C-fibers in pulmonary and cardiovascular reflexes and in isolating C-fiber-mediated reflex responses from those mediated by the release of neuropeptides.
Assuntos
Capsaicina/farmacologia , Neurônios Eferentes/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/inervação , Nervo Vago/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Administração por Inalação , Aerossóis , Anestesia , Animais , Brônquios/efeitos dos fármacos , Brônquios/inervação , Brônquios/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Capsaicina/administração & dosagem , Estimulação Elétrica , Frequência Cardíaca/efeitos dos fármacos , Masculino , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/fisiologia , Ratos , Ratos Wistar , Traqueia/efeitos dos fármacos , Traqueia/inervação , Traqueia/metabolismo , Nervo Vago/citologiaRESUMO
BACKGROUND: Accumulation of immune cell populations and their cytokine products within tracheobronchial airways contributes to the pathogenesis of allergic asthma. It has been postulated that peripheral regions of the lung play a more significant role than proximal airways with regard to inflammatory events and airflow obstruction. OBJECTIVE: To determine whether immune cell populations and associated cytokines are uniformly distributed throughout the conducting airway tree in a non-human primate model of allergic asthma. METHODS: We used a stereologic approach with a stratified sampling scheme to measure the volume density of immune cells within the epithelium and interstitium of trachea and 4-5 intrapulmonary airway generations from house dust mite (HDM) (Dermatophagoides farinae)-challenged adult monkeys. In conjunction with immune cell distribution profiles, mRNA levels for 21 cytokines/chemokines and three chemokine receptors were evaluated at four different airway generations from microdissected lungs. RESULTS: In HDM-challenged monkeys, the volume of CD1a+ dendritic cells, CD4+ T helper lymphocytes, CD25+ cells, IgE+ cells, eosinophils, and proliferating cells were significantly increased within airways. All five immune cell types accumulated within airways in unique patterns of distribution, suggesting compartmentalized responses with regard to trafficking. Although cytokine mRNA levels were elevated throughout the conducting airway tree of HDM-challenged animals, the distal airways (terminal and respiratory bronchioles) exhibited the most pronounced up-regulation. CONCLUSION: These findings demonstrate that key effector immune cell populations and cytokines associated with asthma differentially accumulate within distinct regions and compartments of tracheobronchial airways from allergen-challenged primates.
Assuntos
Asma/imunologia , Citocinas/análise , Sistema Respiratório/imunologia , Animais , Antígenos CD1/imunologia , Antígenos de Dermatophagoides/imunologia , Linfócitos T CD4-Positivos/imunologia , Quimiocinas/análise , Células Dendríticas/imunologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Imunoglobulina E/imunologia , Imuno-Histoquímica/métodos , Macaca mulatta , RNA Mensageiro/análise , Receptores de Quimiocinas/análise , Receptores de Interleucina-2/imunologia , Sistema Respiratório/patologiaRESUMO
Since the original work of by Hering and Breuer in 1868 numerous studies have demonstrated that slowly adapting pulmonary stretch receptors (SARs) are the lung vagal afferents responsible for eliciting the reflexes evoked by moderate lung inflation. SARs play a role in controlling breathing pattern, airway smooth muscle tone, systemic vascular resistance and heart rate. Both anatomical and physiological studies support the contention that SARs, by their close association with airway smooth muscle, continuously sense the tension within the myoelastic components of the airways caused by lung inflation, smooth muscle contraction and/or tethering of small intrapulmonary airways to the lung parenchyma. In addition, intrapulmonary SAR discharge activity is sensitive to changes in P(CO2) within the physiological range. Despite this extensive characterization of SARs, their role in determining breathing pattern and airway tone in individuals with respiratory diseases is only recently being appreciated.