RESUMO
Continuous positive airway pressure (CPAP) administered to tracheostomized rabbits and ferrets for 4 days or 2 wk suppresses bronchial reactivity in vivo and suppresses airway reactivity in lobes and tracheal segments isolated from these animals. In vitro studies of canine tracheal smooth muscle tissues indicate that mechanical loading suppresses the activation of the growth regulatory kinase, Akt, and that Akt is a negative regulator of smooth muscle differentiation. The transduction of mechanical signals in the tracheal tissues in vitro is mediated by integrin-associated adhesion complexes. To determine whether airway responsiveness and Akt activation are modulated by mechanical loads applied for short time periods to the airways of living animals in vivo, mice were mechanically ventilated for 2 h with high (5 cmH2O) or low (0-1 cmH2O) positive end-expiratory pressure (PEEP) and then ventilated at low PEEP for 30 min. Ventilation of mice with PEEP in vivo for 2 h depressed airway responsiveness to methacholine measured in vivo subsequent to the PEEP treatment. Airway narrowing in vitro in intraparenchymal airways in isolated lung slices and contractile responses of isolated tracheal segments in vitro were suppressed for at least 6 h subsequent to the in vivo exposure to PEEP. Tracheal segments isolated from high PEEP-treated mice exhibited significantly lower levels of Akt activation than tracheae from low PEEP-treated mice. The results indicate that mechanical loads imposed in vivo result in physiological and biochemical changes in the airway tissues after a relatively short 2-h period of in vivo loading.
Assuntos
Resistência das Vias Respiratórias , Pulmão/fisiopatologia , Mecanotransdução Celular , Músculo Liso/fisiopatologia , Proteína Oncogênica v-akt/metabolismo , Respiração com Pressão Positiva , Adaptação Fisiológica , Animais , Módulo de Elasticidade , Complacência Pulmonar , Camundongos , Camundongos Endogâmicos C57BL , Estresse MecânicoRESUMO
We present a new one-dimensional model of gas transport in the human adult lung. The model comprises asymmetrically branching airways, and heterogeneous interregional ventilation. Our model differs from previous models in that we consider the asymmetry in both the conducting and the acinar airways in detail. Another novelty of our model is that we use simple analytical relationships to produce physiologically realistic models of the conducting and acinar airway trees. With this new model, we investigate the effects of airway asymmetry and heterogeneous interregional ventilation on the phase III slope in multibreath washouts. The model predicts the experimental trend of the increase in the phase III slope with breath number in multibreath washout studies for nitrogen, SF(6) and helium. We confirm that asymmetrical branching in the acinus controls the magnitude of the first-breath phase III slope and find that heterogeneous interregional ventilation controls the way in which the slope changes with subsequent breaths. Asymmetry in the conducting airways appears to have little effect on the phase III slope. That the increase in slope appears to be largely controlled by interregional ventilation inhomogeneities should be of interest to those wishing to use multibreath washouts to detect the location of the structural abnormalities within the lung.
Assuntos
Pulmão/anatomia & histologia , Pulmão/fisiologia , Modelos Biológicos , Ventilação Pulmonar , Adulto , HumanosRESUMO
The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls. Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers; 38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe; lung volumes and tissue density were also measured. The relationship between airway size and airway generation differed between the CLDI and full-term groups; the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects. Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI.
Assuntos
Displasia Broncopulmonar/diagnóstico por imagem , Medidas de Volume Pulmonar/métodos , Pulmão/diagnóstico por imagem , Pulmão/crescimento & desenvolvimento , Tomografia Computadorizada por Raios X/métodos , Fatores Etários , Displasia Broncopulmonar/fisiopatologia , Pré-Escolar , Doença Crônica , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Terapia Intensiva Neonatal , Pulmão/fisiopatologia , Masculino , Respiração Artificial , Índice de Gravidade de DoençaRESUMO
Previous studies have demonstrated that chronic mechanical strain produced by continuous positive airway pressure (CPAP) reduces in vivo airway reactivity in rabbits and ferrets. For CPAP to potentially have a therapeutic benefit for asthmatic subjects, the reduction in airway responsiveness would need to persist for 12-24 h after its discontinuation, require application for only part of the day, and be effective in the presence of atopic airway inflammation. In the present study, airway responsiveness to acetylcholine or methacholine was measured during mechanical ventilation following three different protocols in which active, nonanesthetized, tracheotomized rabbits were treated with High vs. Low CPAP (6 vs. 0 cmH(2)O). 1) High CPAP was applied continuously for 4 days followed by 1 day of Low CPAP; 2) High CPAP was applied at night and Low CPAP during the daytime for 4 days, and 3) High CPAP was applied for 4 days in animals following ovalbumin (Ova) sensitization and challenge. For all three protocols, treatment with High CPAP resulted in significantly reduced airway responsiveness compared with treatment with Low CPAP. Cumulatively, our in vivo results in rabbits suggest that high CPAP, even when applied only at night, produces a persistent reduction of airway responsiveness. In addition, CPAP reduces airway responsiveness even in the presence of atopic airway inflammation.
Assuntos
Alérgenos , Asma/terapia , Hiper-Reatividade Brônquica/terapia , Pressão Positiva Contínua nas Vias Aéreas , Acetilcolina/farmacologia , Resistência das Vias Respiratórias/fisiologia , Animais , Asma/etiologia , Asma/fisiopatologia , Fenômenos Biomecânicos , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Broncoconstritores/farmacologia , Hipersensibilidade Imediata/fisiopatologia , Imuno-Histoquímica , Masculino , Ovalbumina/imunologia , CoelhosRESUMO
Chronic lung disease of infancy (CLDI) remains a common outcome among infants born extremely prematurely. In older children and adults with lung disease, pulmonary function and computed tomography (CT) scores are used to follow up respiratory disease and assess disease severity. For infants and toddlers, however, these outcomes have been used very infrequently and most often, a dichotomous respiratory outcome (presence or absence of CLDI) is employed. We evaluated the performance of CT score and pulmonary function to differentiate infants and toddlers with CLDI from a control group. CT scans, forced expiratory flows and pulmonary diffusing capacity were obtained in 39 CLDI patients and 41 controls (aged 4-33 months). CT scans were quantified using a scoring system, while pulmonary function was expressed as Z-scores. CT score outperformed pulmonary function in identifying those with CLDI. There were no significant correlations between CT score and pulmonary function. CT score had a better performance than pulmonary function in differentiating individuals with CLDI; however, these outcomes may reflect differing components of the pulmonary pathophysiology of CLDI. This new information on pulmonary outcomes can assist in designing studies with these parameters. Future studies will be required to evaluate which of the outcomes can better detect improvement with therapeutic intervention and/or lung growth.
Assuntos
Displasia Broncopulmonar/diagnóstico por imagem , Displasia Broncopulmonar/fisiopatologia , Fluxo Expiratório Forçado , Capacidade de Difusão Pulmonar/métodos , Tomografia Computadorizada por Raios X/métodos , Criança , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pulmão/diagnóstico por imagem , Pulmão/crescimento & desenvolvimento , Pulmão/fisiologia , Masculino , Capacidade de Difusão Pulmonar/normas , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/normasRESUMO
Infants with recurrent wheeze have repeated episodes of airways obstruction; however, relatively little is known about the structure and function of their lungs when not symptomatic. The current authors evaluated whether infants with recurrent wheeze have smaller airway lumens or thickened airway walls, as well as decreased airway function. High-resolution computed tomography images 1 mm thick were obtained at three anatomic locations at an elevated lung volume and at functional residual capacity. Forced expiratory flows were also measured in subjects with recurrent wheeze. Airway lumen, wall areas and lung tissue density were not significantly different for recurrent wheeze (n = 17) and control (n = 14) subjects; however, subjects with recurrent wheeze had lower forced expiratory flows than predicted. Similar findings were obtained when subjects were grouped by exposure to tobacco smoke. These findings indicate that infants with recurrent wheeze, as well as exposure to tobacco smoke, have lower airway function when not symptomatic. The lower forced expiratory flows may result from a degree of airway narrowing that could not be resolved with the methodology employed or from other mechanisms, such as more collapsible airways or decreased pulmonary elastic recoil.
Assuntos
Pulmão/patologia , Pulmão/fisiopatologia , Sons Respiratórios/diagnóstico , Sons Respiratórios/fisiopatologia , Índice de Massa Corporal , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Pulmão/diagnóstico por imagem , Masculino , Recidiva , Testes de Função Respiratória , Sons Respiratórios/etiologia , Poluição por Fumaça de Tabaco , Tomografia Computadorizada por Raios XRESUMO
The mechanical stress imposed on the lungs during breathing is an important modulator of airway responsiveness in vivo. Our recent study demonstrated that continuous positive airway pressure applied to the lungs of nonanesthetized, tracheotomized rabbits for 4 days decreased lower respiratory system responsiveness to challenge with ACh (Xue Z, Zhang L, Ramchandani R, Liu Y, Antony VB, Gunst SJ, Tepper RS. J. Appl Physiol 99: 677-682, 2005). In addition, airway segments excised from the lungs of these animals and studied in vitro exhibited reduced contractility. However, the mechanism for this reduction in contractility was not determined. The stress-induced decrease in airway responsiveness could have resulted from alterations in the excitation-contraction coupling mechanisms of the smooth muscle cells, or it might reflect changes in the structure and/or composition of the airway wall tissues. In the present study, we assessed the effect of prolonged chronic stress of the lungs in vivo on airway smooth muscle force generation, myosin light chain phosphorylation, and airway wall structure. To enhance the potential development of stress-induced structural changes, we applied mechanical stress for a prolonged period of time of 2-3 wk. Our results demonstrate a direct connection between the decreased airway responsiveness caused by chronic mechanical stress of the lungs in vivo and a persistent decrease in contractile protein activation in the airway smooth muscle isolated from those lungs. The chronic stress also caused an increase in airway size but no detectable changes in the composition of the airway wall.
Assuntos
Resistência das Vias Respiratórias , Pressão Positiva Contínua nas Vias Aéreas , Pulmão/fisiopatologia , Contração Muscular , Músculo Liso/fisiopatologia , Traqueia/fisiopatologia , Acetilcolina/administração & dosagem , Administração por Inalação , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Testes de Provocação Brônquica , Broncoconstritores/administração & dosagem , Relação Dose-Resposta a Droga , Furões , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Cloreto de Metacolina/administração & dosagem , Contração Muscular/efeitos dos fármacos , Força Muscular , Músculo Liso/diagnóstico por imagem , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Cadeias Leves de Miosina/metabolismo , Fosforilação , Estresse Mecânico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem , Traqueia/efeitos dos fármacos , Traqueia/metabolismo , Traqueia/cirurgiaRESUMO
Active, nonanesthetized, tracheotomized rabbits were subjected to continuous positive airway pressure (CPAP) for 4 days to determine the effects of chronic mechanical strain on lung and airway function. Rabbits were maintained for 4 days at a CPAP of 6 cmH(2)O (high CPAP), at a CPAP of 0 cmH(2)O (low CPAP), or without tracheostomy (no CPAP). After treatment with CPAP, changes in respiratory resistance in response to increasing concentrations of inhaled ACh were measured during mechanical ventilation to evaluate respiratory system responsiveness in vivo. Intraparenchymal bronchial segments were isolated from the lungs of all animals to evaluate airway smooth muscle responsiveness and bronchial compliance in vitro. Rabbits maintained for 4 days at high CPAP demonstrated significantly lower responsiveness to ACh compared with rabbits that were maintained at low CPAP or with no CPAP. Airways isolated from the lungs of animals subjected to the chronic application of high CPAP were also less responsive to ACh in vitro than the airways isolated from animals subjected to low CPAP or no CPAP. The persistence of the decreased responsiveness in the excised airway tissues suggests that the decreased respiratory system responsiveness observed in vivo results primarily from direct effects on the airways. The results demonstrate that the application of prolonged mechanical strain in vivo can reduce airway reactivity.
Assuntos
Pulmão/fisiologia , Respiração com Pressão Positiva/métodos , Ventilação Pulmonar/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Acetilcolina , Adaptação Fisiológica/fisiologia , Animais , Relação Dose-Resposta a Droga , Pulmão/efeitos dos fármacos , Ventilação Pulmonar/efeitos dos fármacos , Coelhos , Testes de Função Respiratória , Volume de Ventilação Pulmonar/efeitos dos fármacosRESUMO
Pathophysiological conditions of the lung may shift the balance of forces so as to chronically alter the amount of strain imposed on the airways. This chronic strain could result in changes in the structure and/or function of the airways that affect its physiological properties. We evaluated the effects of imposing physiological levels of chronic mechanical strain on the passive and active physiological properties of intraparenchymal rabbit airways. Isolated bronchial segments were cultured for 48 h at transmural pressures of 0 cmH(2)O (No Strain) or 7 cmH(2)O (Strain). Effects of strain on small parenchymal airways were evaluated in lung tissue slices cultured under conditions of No Strain or approximately 50% increased in diameter (Strain). Chronic strain resulted in a higher passive compliance of the bronchial segments and larger airway lumen size. In addition, bronchi not subjected to chronic Strain were more responsive to ACh than bronchi subjected to chronic Strain, and airways in lung slices subjected to No Strain narrowed more in response to ACh than airways in lung slices subjected to Strain. The greatest effects of chronic strain occurred in the smallest sized airways. Our results suggest that chronic distension of the airways has physiologically important effects on their passive and active properties, which are most prominent in the smaller, more peripheral airways.
Assuntos
Broncoconstrição/fisiologia , Pulmão/fisiologia , Contração Muscular/fisiologia , Animais , Fenômenos Biomecânicos/métodos , Masculino , Ventilação Pulmonar/fisiologia , Coelhos , Mecânica Respiratória/fisiologia , Estresse MecânicoRESUMO
Immature rabbits have greater maximal airway narrowing with bronchoconstriction in vivo compared with mature animals. As isolated immature lungs have a lower shear modulus, it is unclear whether the greater airway narrowing in the immature lung is secondary to less tethering between the airways and the lung parenchyma or to differences in the mechanical properties of the mature and immature airways. In the present study, we compared the mechanical properties of fluid-filled, isolated, intraparenchymal airway segments of the same generation from mature and immature rabbits. Stimulation with ACh resulted in greater airway narrowing in immature than mature bronchi. The immature bronchi were more compliant, had a lower resting airway volume, and were more collapsible compared with the mature bronchi. When the airways were contracted with ACh under isovolume conditions, the immature bronchi generated greater active pressure, and they were more sensitive to ACh than were mature bronchi. Our results suggest that maturational differences in the structure and function of the airways in the absence of the lung parenchyma can account for the greater maximal narrowing of immature than mature airways in vivo.
Assuntos
Envelhecimento/fisiologia , Brônquios/crescimento & desenvolvimento , Brônquios/fisiologia , Broncoconstrição/fisiologia , Traqueia/crescimento & desenvolvimento , Traqueia/fisiologia , Acetilcolina/farmacologia , Pressão do Ar , Animais , Cartilagem/fisiologia , Elasticidade , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , CoelhosRESUMO
Exhaled nitric oxide (Fe(NO)) measurements provide a noninvasive approach to the evaluation of airway inflammation. Flow-independent NO exchange parameters [airway NO transfer factor (D(NO)) and airway wall NO concentration (Cw(NO))] can be estimated from Fe(NO) measurements at low flows and may elucidate mechanisms of disturbances in NO exchange. We measured Fe(NO) in sedated infants by using an adaptation of a raised lung volume rapid thoracic compression technique that creates forced expiration through a mass-flow controller that lasts 5-10 s, at a constant preset flow. We measured Fe(NO) at expired flows of 50, 25, and 15 ml/s in five healthy infants (7-31 mo). Median Fe(NO) increased [24, 40, and 60 parts per billion (ppb)] with decreasing expiratory flows (50, 25, and 15 ml/s). Group median (range) for D(NO) and Cw(NO) were 12.7 (3.2-37) x 10(-3) nl. s(-1). ppb(-1) and 108.9 (49-385) ppb, respectively, similar to values reported in healthy adults. Exhaled NO is flow dependent; flow-independent parameters of exhaled NO kinetics can be assessed in infants and are similar to values described in adults.
Assuntos
Testes Respiratórios , Óxido Nítrico , Testes Respiratórios/instrumentação , Testes Respiratórios/métodos , Pré-Escolar , Equipamentos e Provisões , Feminino , Fluxo Expiratório Forçado , Humanos , Lactente , Cinética , Masculino , Boca/fisiologia , Concentração Osmolar , PressãoRESUMO
Volume history is an important determinant of airway responsiveness. In healthy adults undergoing airway challenge, deep inspiration (DI) provides bronchodilating and bronchoprotective effects; however, the effectiveness of DI is limited in asthmatic adults. We hypothesized that, when assessed under similar conditions, healthy infants have heightened airway reactivity compared with healthy adults and that the effectiveness of DI is limited in infants. We compared the effect of DI on reactivity by using full (DI) vs. partial (no DI) forced-expiratory maneuvers on 2 days in supine, healthy nonasthmatic infants (21) and adults (10). Reactivity was assessed by methacholine doses that decreased forced expiratory flow after exhalation of 75% forced vital capacity during a full maneuver and maximal expiratory flow at functional residual capacity during a partial maneuver by 30% from baseline. Reactivity in adults increased when DI was absent, whereas infants' reactivity was unchanged. Infants were more reactive than adults in the presence of DI; however, adult and infant reactivity was similar in its absence. Our findings indicate that healthy infants are more reactive than adults and, like asthmatic adults, do not benefit from DI; this difference may be an important characteristic of airway hyperreactivity.
Assuntos
Envelhecimento/fisiologia , Medidas de Volume Pulmonar , Pulmão/fisiologia , Prontuários Médicos , Adulto , Testes de Provocação Brônquica , Broncoconstritores , Pré-Escolar , Feminino , Fluxo Expiratório Forçado , Humanos , Lactente , Masculino , Cloreto de Metacolina , Pessoa de Meia-Idade , Valores de Referência , Mecânica RespiratóriaRESUMO
Immature rabbits have greater maximal airway narrowing and greater maximal fold increases in airway resistance during bronchoconstriction than mature animals. We have previously demonstrated that excised immature rabbit lungs have more distensible airways, a lower shear modulus, and structural differences in the relative composition and thickness of anatomically similar airways. In the present study, we incorporated anatomic and physiological data for mature and immature rabbits into a computational model of airway narrowing. We then investigated the relative importance of maturational differences in these factors as determinants of the greater airway narrowing that occurs in the immature animal. The immature model demonstrated greater sensitivity to agonist, as well as a greater maximal fold increase in airway resistance. Exchanging values for airway compliance between the mature and immature models resulted in the mature model exhibiting a greater maximal airway response than the immature model. In contrast, exchanging the shear moduli or the composition of the airway wall relative to the airway size produced relatively small changes in airway reactivity. Our results strongly suggest that the mechanical properties of the airway, i.e., greater compliance of the immature airway, can be an important factor contributing to the greater airway narrowing of the immature animal.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Pulmão/fisiologia , Modelos Biológicos , Mecânica Respiratória/fisiologia , Acetilcolina/farmacologia , Fatores Etários , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Asma/fisiopatologia , Relação Dose-Resposta a Droga , Humanos , Pulmão/crescimento & desenvolvimento , Músculo Liso/fisiologia , Coelhos , Mecânica Respiratória/efeitos dos fármacosRESUMO
The repair of an injured bronchial epithelial cell (BEC) monolayer requires proliferation and migration of BECs into the injured area. We hypothesized that BEC monolayer injury results in monocyte chemoattractant protein-1 (MCP-1) production, which initiates the repair process. BECs (BEAS-2B from ATCC) were utilized in this study. MCP-1 interacts with CCR2B receptor (CCR2B), resulting in cell proliferation, haptotaxis, and healing of the monolayer. Reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to verify the presence of CCR2B. CCR2B was not merely present but also inducible by interleukin-2 (IL-2) and lipopolysaccharide (LPS). We demonstrated by immunohistochemistry that BECs express MCP-1 after injury and that receptor expression can be regulated by exposure to IL-2 and LPS. Haptotactic migration of cells was enhanced in the presence of MCP-1 and reduced in the presence of CCR2B antibody. This enhanced or depressed ability of the BECs to perform haptotactic migration was shown to be statistically significant (P < 0.05) when compared to controls. Finally, BECs proliferate in response to MCP-1 as proven by electric cell-substrate impedance sensing (ECIS) technology. MCP-1-specific antibodies were shown to neutralize the MCP-1-mediated BEC proliferation. This cascade of events following injury to the bronchial epithelium may provide insight into the mechanism of the repair process.
Assuntos
Brônquios/citologia , Quimiocina CCL2/fisiologia , Células Epiteliais/patologia , Divisão Celular , Linhagem Celular Transformada , Movimento Celular , Quimiocina CCL2/biossíntese , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Interleucina-2/farmacologia , Lipopolissacarídeos/farmacologia , Receptores CCR2 , Receptores de Quimiocinas/efeitos dos fármacos , Receptores de Quimiocinas/fisiologiaRESUMO
Methacholine (MCh)-induced bronchoconstriction in vivo produces greater maximal increases in pulmonary and airway resistances in immature than in mature rabbits. Our recent findings of lower shear modulus and greater airway distensibility suggest a lower elastic load limiting airway smooth muscle (ASM) shortening in immature rabbit lungs. We hypothesized that a lower elastic load should result in greater velocity of airway narrowing. Lung explants were prepared from three immature and five mature rabbits. Dynamic narrowing of intraparenchymal airways after maximal MCh stimulation was assessed by video microscopy. Immature airways (n = 80) compared with mature airways (n = 110) demonstrated greater peak velocity of shortening (6.98 +/- 0.32 versus 4.22 +/- 0.18% of baseline perimeter/s) and greater maximal airway narrowing, expressed as percentage of baseline area (31.9 +/- 1.6 versus 42.2 +/- 1.8%). For both groups, a greater velocity of shortening resulted in greater airway narrowing. As available data do not support maturational differences in rabbit ASM, our results are consistent with a lower elastic load limiting ASM shortening in the immature rabbit.
Assuntos
Broncoconstrição/fisiologia , Desenvolvimento Muscular , Músculo Liso/crescimento & desenvolvimento , Fatores Etários , Animais , Técnicas de Cultura , Elasticidade , Pulmão/crescimento & desenvolvimento , Coelhos , Fatores de TempoRESUMO
The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.
Assuntos
Brônquios/efeitos dos fármacos , Brônquios/fisiologia , Broncoconstritores/farmacologia , Cloreto de Metacolina/farmacologia , Fenômenos Fisiológicos Respiratórios , Envelhecimento/fisiologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Testes de Provocação Brônquica , Broncoconstrição/fisiologia , Coelhos , Volume de Ventilação PulmonarRESUMO
UNLABELLED: Several studies have demonstrated that normal infants exhibit bronchoconstriction after inhalation of nonspecific agonists and that the induced airway narrowing can be reversed by the inhalation of a beta-agonist. However, there are very limited data on baseline airway tone and the airway response to a beta-agonist in this subject population. The purpose of our study was to evaluate in normal infants baseline airway responsiveness to the inhaled beta-agonist, albuterol, using changes in maximal expiratory flows. Forty-one healthy infant volunteers with no history of respiratory disease or recurrent wheezing (ages 5.4 to 141.4 wk) were studied. Maximal expiratory flow- volume curves were obtained at baseline and 10 min after inhalation of albuterol (n = 28) or placebo (n = 13) using a metered-dose inhaler with a spacer. The mean percent change was significantly greater (p < 0.05) in the albuterol versus placebo group for FEV(0.5) (2.2% versus -1.5%), FEF(75%) (10.6% versus -3.1%), and FEF(85%) (12.9% versus 0.5%). Six of 28 albuterol-treated infants demonstrated increases in FEF(75%) greater than two standard deviations from the mean change in FEF(75%) seen in the placebo group. These infants were younger and more frequently exposed to maternal smoking during pregnancy. We conclude that normal healthy infants have overall levels of baseline airway tone that are similar to that reported in adults and older children; however, among the infants we evaluated the response to an inhaled bronchodilator was greatest in the youngest infants and in those exposed to tobacco smoking. KEYWORDS: airway responsiveness; asthma; tobacco smoke; infant pulmonary function; bronchodilator
Assuntos
Resistência das Vias Respiratórias/fisiologia , Albuterol/farmacologia , Broncodilatadores/farmacologia , Poluição por Fumaça de Tabaco/efeitos adversos , Administração por Inalação , Adulto , Feminino , Fluxo Expiratório Forçado , Humanos , Lactente , Recém-Nascido , Masculino , GravidezRESUMO
The purpose of this study was to evaluate spirometric lung function in normal children ages 3 to 6 yr. Spirometric measurements were obtained at nursery and daycare centers by experienced pediatric pulmonary function technicians. Of 307 children recruited, 259 fulfilled our criteria as normal. Of these, 82.6% (214) were able to perform technically acceptable and reproducible maneuvers during a testing session limited to 15 min. The regression model with log-transformed parameters of pulmonary function and height had the best correlations. After accounting for height in the model, other physical traits and health questionnaire items did not contribute significantly. PEFR, FVC, FEV1, and FEF25-75 all increased with increasing height; correlation coefficients were 0.73, 0.93, 0.92, and 0.67, respectively. The group mean coefficients of variation for replicate measurements of PEFR, FVC, FEV1, and FEF25-75 were 7.8%, 2.5%, 2.7%, and 8.3%, respectively. There was a significant decrease in the ratio FEV1/FVC with increasing height; the mean predicted FEV1/FVC was 0.97 at 90 cm height and 0.89 at 125 cm height. In conclusion, reproducible spirometry can be obtained in the majority of preschool children and has the potential to improve our assessment and management of pulmonary disease.
Assuntos
Espirometria , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Ventilação Pulmonar , Valores de ReferênciaRESUMO
The scheme of Horsfield et al. for describing the pulmonary airway tree (J Appl Physiol 52: 21-26, 1982) catalogs each airway according to its order and the difference in order of its two daughters (denoted Delta). Although this scheme captures the natural asymmetry in the airway tree, it is still deterministic, because it assumes that all airways of a given order are the same; yet such variability is extremely important in determining the overall behavior of the lungs. We therefore analyzed complete lung lobes from three mature and two immature rabbits and determined the Horsfield order and Delta of every airway down to the terminal bronchioles. We also measured the diameter of each airway. This allowed us to determine the average structure of the rabbit airway tree, the variation about this average, and also how the structures of mature and immature airway trees compare. We found some variation in branching asymmetry and airway diameter at a given order between animals but no evidence of systematic differences in structure between mature and immature lungs. We found evidence of a difference in the branching structure of the peripheral vs. the central part of the airway tree (the break point being around order 20). We also determined the nature of the variation in Delta and diameter as a function of order, which should be valuable for the development of computer models seeking to encapsulate the naturally occurring regional variation in airway geometry in the normal rabbit lung.
Assuntos
Pulmão/anatomia & histologia , Pulmão/crescimento & desenvolvimento , Animais , Brônquios/anatomia & histologia , Brônquios/crescimento & desenvolvimento , Modelos Anatômicos , CoelhosRESUMO
We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs.