RESUMEN
In 1996, the Future of Pediatric Education (FOPE) Project of the American Academy of Pediatrics (AAP) developed surveys to describe the nature of pediatric practices, recent trends in clinical practice, and anticipated workforce needs for both pediatric generalists and pediatric sub-specialists. A survey was specifically developed to describe the features of pediatric pulmonology as self-reported by pediatric pulmonologists. The survey was distributed to members of the AAP Pulmonology Section, the Pediatric Assembly of the American Thoracic Society, and certified pediatric pulmonologists recognized by the American Board of Pediatrics. Of the 535 respondents (67% of those invited to respond), the responses of 388 certified and 94 trained but not board-certified pulmonologists were included in the results. The characteristics of certified and non-certified respondents were the same for most survey questions. Clinical activities occupy 73 +/- 29% of professional time. Most pulmonologists work in urban, inner city, or suburban settings and 85% are affiliated with a medical school. One third are in private practice. As a group, research activities occupy less than 15% of their time. Most pediatric pulmonologists maintain a referral practice and use physician extenders to provide care. Patients with asthma and cystic fibrosis comprise 60-70% of patient volume. Both the volume and complexity of patients are increasing, as is competition for pediatric sub-specialty services. Pediatric pulmonary practices vary in size and in volume of patients that they manage in various settings. Forty percent of respondents identify allergists and other pediatric pulmonologists as sources of competition. Sixty-nine percent of respondents do not believe that there is a current need for additional pediatric pulmonologists in their respective communities. Only 15% of respondents plan to retire in the next decade.
Asunto(s)
Pediatría , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neumología , Adulto , Anciano , Educación Médica , Femenino , Predicción , Encuestas de Atención de la Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Pediatría/educación , Pediatría/tendencias , Neumología/educación , Neumología/tendencias , Recursos Humanos , Carga de TrabajoAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Virus Sincitiales Respiratorios/inmunología , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Palivizumab , Factores de RiesgoRESUMEN
OBJECTIVES: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. DESIGN: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed. RESULTS: Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function. CONCLUSIONS: Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasas/uso terapéutico , Adolescente , Adulto , Aerosoles , Anciano , Formación de Anticuerpos , Hiperreactividad Bronquial/inducido químicamente , Niño , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Desoxirribonucleasas/administración & dosificación , Desoxirribonucleasas/inmunología , Esquema de Medicación , Hipersensibilidad a las Drogas/etiología , Disnea/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Inmunoglobulina G/biosíntesis , Isotipos de Inmunoglobulinas/biosíntesis , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Calidad de Vida , Proteínas Recombinantes , Seguridad , Capacidad Vital/efectos de los fármacosRESUMEN
Respiratory input impedance (Zin) is a potentially informative test of pulmonary function in infants who are unable to perform standard tests commonly performed in children and adults Analysis of Zin in dogs using the six-element model of DuBois et al. (J Appl Physiol 8:587, 1956) provides estimates of airways resistance separate from tissue resistance, as well as an estimate of thoracic gas volume. However, reliable estimates of these parameters can only be obtained when Zin displays a distinct antiresonance that is associated with the tissue inertance and alveolar gas compression compliance. To determine whether infants have such an antiresonance. Zin was measured in nine healthy infants (4 < f < 160 Hz). An antiresonance was found at 112.8-10.4 Hz, and the six-element model fit these data well, but the resulting parameters were physiologically unrealistic. We hypothesized that the antiresonance in the measured Zin is the result of shunt compliance proximal to alveolar gas compression compliance. Gas compression in the face mask and nonrigid upper airway walls could provide such a shunt compliance. We investigated another model with four parameters, a single shunt compliance (Cim) representing gas compression in the face mask in parallel with the infant's total respiratory resistance (Rrs) inertance (Irs), and compliance (Crs). This model fits the data well, and the estimated R, (19.3, 4.2 cmH O/L/s) was physiologically reasonable. However, Crs (Crs 1.03-0.58 mL cmH2O) was one order of magnitude smaller than reported Crs. The value for Cim was slightly larger than that based on the estimated volume of gas in the face mask, suggesting an additional influence of upper airway wall shunting. Computer simulations using a model that includes the face mask and upper airway walls confirmed that Cim and the upper airway wall properties significantly influence Zin data over this frequency range. Nevertheless, these simulations suggest that the Rrs estimated from the four-element model is related to airway resistance.
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Resistencia de las Vías Respiratorias/fisiología , Mecánica Respiratoria/fisiología , Preescolar , Simulación por Computador , Femenino , Humanos , Lactante , Rendimiento Pulmonar/fisiología , Masculino , Pruebas de Función RespiratoriaRESUMEN
Elastin degradation has been reported to be increased in patients with cystic fibrosis (CF). In order to further explore evidence for elastin degradation in a group of 18 patients with CF with a wide range of disease severity, we used an isotope dilution method to measure urinary desmosine (DES) and isodesmosine (IDES), amino acids derived exclusively from cross-linked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), amino acids derived exclusively from cross-linked collagen. Urinary DES and IDES (mean +/- SD) were 23.9 +/- 30.7 and 18.5 +/- 22.4 micrograms/g creatinine, respectively, in the patients with CF versus 7.5 +/- 1.7 and 6.8 +/- 1.4 micrograms/g creatinine, respectively, in 10 healthy control subjects (p < 0.001); only two patients with CF had DES values within the control range. The values of urinary HP and LP in the CF group were 54.9 +/- 39.1 and 12.3 +/- 8.6 nmol/mmol creatinine, respectively, versus 24.5 +/- 5.8 and 5.1 +/- 2.7 nmol/mmol creatinine, respectively, in the controls (p < 0.005). Both HP and LP were highly correlated (r = 0.71, p < 0.0001). Patients with CF had active pulmonary inflammation; neutrophils were abundant in the bronchoalveolar lavage fluid of the CF group and correlated with elastase activity measured with methoxysuccinyl Ala-Ala-Pro-Val paranitroanilide (r = 0.61, p < 0.05). Airway neutrophils had decreased expression of the complement receptor CR1 (CR1/CR3 of 0.17 +/- 0.15 versus 1.0 for blood neutrophils), a change known to be caused by uninhibited neutrophil elastase. We conclude that lung elastin is the most likely source of the increased DES and IDES in CF.
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Aminoácidos/orina , Colágeno/metabolismo , Fibrosis Quística/orina , Elastina/metabolismo , Adulto , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Fibrosis Quística/metabolismo , Desmosina/orina , Femenino , Humanos , Isodesmosina/orina , Elastasa de Leucocito , Masculino , Neutrófilos/química , Elastasa Pancreática/análisis , Receptores de Complemento/análisisRESUMEN
BACKGROUND/AIMS: Hepatobiliary disease is the second most common cause of mortality in patients with cystic fibrosis (CF). In the liver, only the intrahepatic biliary epithelial (IBE) cells express cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The aim of this study was to determine whether human CF-derived IBE cells can be infected with adenovirus and the CF phenotype complemented. METHODS: IBE cells were isolated from 2 patients with CF and immortalized using retrovirus transduction of SV40 large T antigen. Immortalized cells were infected with the adenovirus vector Ad2/CFTR2 and assayed 2-31 days postinfection for cyclic adenosine monophosphate (cAMP)-induced halide efflux. Halide efflux was measured in single cells using fluorescence microscopy and the fluorescent probe 6-methoxy-N-(3-sulfopropyl)-quinolinium. RESULTS: CF-derived IBE cell lines express biliary specific markers and express no cAMP-inducible halide efflux. Following infection with the adenovirus vector Ad2/CFTR2, a cAMP-induced halide efflux was observed for 31 days, although the number of responsive cells decreased with time. CONCLUSIONS: Human CF-IBE cells can be infected by adenovirus and the defective CFTR complemented. The loss of responsive cells with time could be due to loss of construct and/or a reduced growth of cells that are overexpressing CFTR. These CF-IBE cell lines offer an opportunity to determine the mechanisms responsible for hepatobiliary disease in the patients with CF.
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Conductos Biliares/metabolismo , Fibrosis Quística/terapia , Terapia Genética , Proteínas de la Membrana/genética , Células 3T3 , Animales , Línea Celular , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Epitelio , Prueba de Complementación Genética , Vectores Genéticos , Humanos , Ratones , TransfecciónAsunto(s)
Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasa I/uso terapéutico , Expectorantes/uso terapéutico , Adulto , Niño , Ensayos Clínicos como Asunto , Desoxirribonucleasa I/administración & dosificación , Desoxirribonucleasa I/efectos adversos , Humanos , Lactante , Nebulizadores y Vaporizadores , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéuticoRESUMEN
Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro. To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expiratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) across all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0.001). rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being. No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some patients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNase to pediatric and adult outpatients with CF improves lung function and is well tolerated. Although all three doses were efficacious, the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasa I/administración & dosificación , Adolescente , Adulto , Aerosoles , Análisis de Varianza , Distribución de Chi-Cuadrado , Fibrosis Quística/epidemiología , Fibrosis Quística/fisiopatología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Calidad de Vida , Factores de TiempoRESUMEN
BACKGROUND: Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections. METHODS: Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored. RESULTS: In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration. CONCLUSIONS: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.
Asunto(s)
Bronquitis/tratamiento farmacológico , Fibrosis Quística/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Tobramicina/administración & dosificación , Adolescente , Aerosoles , Bronquitis/microbiología , Bronquitis/fisiopatología , Fibrosis Quística/fisiopatología , Método Doble Ciego , Femenino , Humanos , Masculino , Monitoreo Fisiológico , Infecciones por Pseudomonas/fisiopatología , Mecánica Respiratoria , Tobramicina/uso terapéuticoRESUMEN
Traditionally, DNA used for PCR-based diagnostic analysis has originated from white cells fractionated from whole blood. Although this method yields substantial quantities of DNA, there are some drawbacks to the procedure, including the inconvenience of drawing blood, risk of exposure to blood-borne pathogens, liquid sample handling, and the somewhat involved extraction procedure. Alternatively, DNA for genetic diagnosis has been derived from finger stick blood samples, hair roots, cheek scrapings, and urine samples. Oral saline rinses have also been used extensively as a means of collecting buccal epithelial cells as a DNA source. However, this method still requires liquid sample handling. Herein, we present our results involving the rapid extraction of DNA from buccal cells collected on cytology brushes and swabs for use in PCR reactions, specifically the multiplex amplification of 5 exons within the CFTR gene. The quality of DNA isolated from buccal cells, collected in this manner, has been sufficient to reproducibly support multiplex amplification. Cheek cell samples and the DNA prepared from them as described here are highly stable. The success rate of PCR amplification on DNA prepared from buccal cells is 99%. In a blind study comparing the analysis of 12 mutations responsible for cystic fibrosis in multiplex products amplified with DNA from both blood and buccal cell samples from 464 individuals, there was 100% correlation of results for blood and cheek cell DNA, validating the use of DNA extracted from cheek cells collected on cytology brushes for use in genetic testing.
Asunto(s)
Análisis Mutacional de ADN , Proteínas de la Membrana/genética , Mucosa Bucal/citología , Reacción en Cadena de la Polimerasa , Secuencia de Bases , Mejilla , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Fibrosis Quística/prevención & control , Regulador de Conductancia de Transmembrana de Fibrosis Quística , ADN/sangre , Análisis Mutacional de ADN/instrumentación , Estudios de Factibilidad , Pruebas Genéticas , Humanos , Datos de Secuencia Molecular , Método Simple Ciego , Manejo de EspecímenesRESUMEN
Continuous epithelial cell lines from individuals with cystic fibrosis (CF) and normal controls are required to understand the genetic and cellular defects in CF. We used retroviruses to transduce SV40 large T antigen into nasal epithelial cells. Transformed continuous cell lines were isolated that expressed epithelial markers, cytokeratin, and tight junctions. Northern blot analysis shows that all of the cell lines express the putative CF gene mRNA. Studies of transepithelial electrolyte transport show that CF and normal cell lines develop a transepithelial electrical resistance. Normal but not CF cell lines secreted Cl- in response to agonists that increase cellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) (isoproterenol, forskolin, and a membrane-permeant analogue of cAMP) or in response to a tumor-promoting phorbol ester that activates protein kinase C. In contrast, the Ca2(+)-elevating agonist bradykinin and the Ca2+ ionophore A23187 stimulated secretion in both normal and CF cell lines. The continuous cell lines we have produced maintain their proper phenotypes and will serve as useful tools in understanding the pathophysiology of CF.
Asunto(s)
Fibrosis Quística/genética , Antígenos Transformadores de Poliomavirus/genética , Secuencia de Bases , Biomarcadores , Proteínas Sanguíneas/genética , Bradiquinina/farmacología , Calcimicina/farmacología , Calgranulina A , Línea Celular , Transformación Celular Neoplásica , Células Cultivadas , Canales de Cloruro , Cloruros/metabolismo , Colforsina/farmacología , Fibrosis Quística/patología , Fibrosis Quística/fisiopatología , Células Epiteliales , Epitelio/fisiología , Genotipo , Humanos , Canales Iónicos/efectos de los fármacos , Canales Iónicos/fisiología , Queratinas/análisis , Potenciales de la Membrana/efectos de los fármacos , Proteínas de la Membrana/fisiología , Datos de Secuencia Molecular , Mucosa Nasal/citología , Mucosa Nasal/patología , Mucosa Nasal/fisiología , Sondas de Oligonucleótidos , Fenotipo , Reacción en Cadena de la Polimerasa , Valores de Referencia , Retroviridae/genética , Virus 40 de los Simios/genética , Acetato de Tetradecanoilforbol/farmacología , Teofilina/farmacologíaRESUMEN
We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.
Asunto(s)
Resistencia de las Vías Respiratorias , Asma/fisiopatología , Fibrosis Quística/fisiopatología , Nitrógeno , Adolescente , Adulto , Resistencia de las Vías Respiratorias/efectos de los fármacos , Albuterol/farmacología , Bronquios/efectos de los fármacos , Bronquios/fisiología , Niño , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Valores de ReferenciaRESUMEN
For respiratory system impedance (Zrs), the six-element model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) suggests three resonant frequencies (f1,f2,f3), where f1 is the result of the sum of tissue and airway inertances and tissue compliance and f2 is the result of alveolar gas compression compliance (Cg) and tissue inertance (Iti). Three such resonant frequencies have been reported in humans. However, the parameter estimates resulting from fitting this model to the data suggested that f2 and f3 were not associated with Cg and Iti but with airway acoustic properties. In the present study, we measured Zrs between 5 and 320 Hz in 10 healthy adult humans breathing room air or 80% He-20% O2 (HeO2) to gain insight as to whether airway or tissue properties are responsible for the f2 and f3. When the subjects breathed room air, f2 occurred at 170 +/- 16 (SD) Hz, and when they breathed HeO2 it occurred at 240 +/- 24 Hz. If this resonance were due to Cg and Iti it should not have been affected to this extent by the breathing of HeO2. We thus conclude that f2 is not due to tissue elements but that it is an airway acoustic resonance. Furthermore, application of the six-element model to analyze Zrs data at these frequencies is inappropriate, and models incorporating the airway acoustic properties should be used. One such model is based on the concept of equivalent length, which is defined as the length of an open-ended, cylindrical tube that has the same fundamental acoustic resonant frequency.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Mecánica Respiratoria/fisiología , Adulto , Resistencia de las Vías Respiratorias/fisiología , Femenino , Humanos , Rendimiento Pulmonar/fisiología , Masculino , Persona de Mediana EdadRESUMEN
Recent studies on respiratory impedance (Zrs) have predicted that at frequencies greater than 64 Hz a second resonance will occur. Furthermore, if one intends to fit a model more complicated than the simple series combination of a resistance, inertance, and compliance to Zrs data, the only way to ensure statistically reliable parameter estimates is to include data surrounding this second resonance. An additional question, however, is whether the resulting parameters are physiologically meaningful. We obtained input impedance data from eight healthy adult humans using discrete frequency forced oscillations from 4 to 200 Hz. Three resonant frequencies were seen: 8 +/- 2, 151 +/- 10, and 182 +/- 16 Hz. A seven-parameter lumped element model provided an excellent fit to the data in all subjects. This model consists of an airway resistance (Raw), which is linearly dependent on frequency, and airway inertance separated from a tissue resistance, inertance, and compliance by a shunt compliance (Cg) thought to represent gas compressibility. Model estimates of Raw and Cg were compared with those suggested by measurement of Raw and thoracic gas volume using a plethysmograph. In all subjects the model Raw and Cg were significantly lower than and not correlated with the corresponding plethysmographic measurement. We hypothesize that the statistically reliable but physiologically inconsistent parameters are a consequence of the distorting influence of airway wall compliance and/or airway quarter-wave resonance. Such factors are not inherent to the seven-parameter model.
Asunto(s)
Resistencia de las Vías Respiratorias , Modelos Biológicos , Respiración , Adulto , Femenino , Humanos , MasculinoRESUMEN
Mechanical parameters of the respiratory system are often estimated from respiratory impedances using lumped-element inverse models. One such six-element model is composed of an airway branch [with a resistance (Raw) and inertance (Iaw)] separated from a tissue branch [with a resistance (Rt), inertance (It), and compliance (Ct)] by a shunt compliance representing alveolar gas compression (Cg). Even though the airways are known to have frequency-dependent resistance and inertance, these inverse models have been composed of linear frequency-independent elements. In this study we investigated the use of inverse models where the airway branch was represented by a frequency-independent Raw and Iaw, a Raw that is linearly related to frequency and an Iaw that is independent of frequency, and a system of identical parallel tubes the impedance of which was computed from the tube radius and length. These inverse models were used to analyze airway and respiratory impedances between 2 and 1,024 Hz that were predicted from an anatomically detailed forward model. The forward model represented the airways by an asymmetrically branched network with a terminal impedance representative of known Cg, Rt, It, and Ct. For respiratory impedances between 2 and 128 Hz, all models fit the data reasonably well, and reasonably accurate estimates of Cg, Rt, It, and Ct were extracted from these data. For data above 200 Hz, however, only the multiple-tube model accurately fitted respiratory impedances (Zrs). This model fitted the Zrs data best when composed of 27 tubes, each having a radius of 0.148 cm and a length of 16.5 cm.
Asunto(s)
Fenómenos Fisiológicos Respiratorios , Animales , Perros , Estimulación Eléctrica , Matemática , Modelos BiológicosRESUMEN
To describe the mechanical characteristics of the respiratory system in intubated neonates with respiratory disease, we measured impedance and resistance in six paralyzed intubated infants with respiratory distress syndrome, three of whom also had pulmonary interstitial emphysema. We subtracted the effects of the endotracheal tube after showing that such subtraction was valid. Oscillatory flow was generated from 4 to 40 Hz by a loudspeaker, airway pressure was measured, and flow was calculated from pressure changes in an airtight enclosure mounted behind the flow source (speaker plethysmograph). After subtraction of the endotracheal tube contribution, resistance ranged from 22 to 34 cmH2O liter-1 s; compliance from 0.22 to 0.68 ml/cmH2O; and inertance from 0.0056 to 0.047 cmH2O liter-1 s2. Our results indicate that, for these intubated infants, the mechanics of the respiratory system are well described as resistance, compliance, and inertance in series. Most of the inertance, some of the resistance, and little of the compliance are due to the endotracheal tube. When the contribution of the endotracheal tube is subtracted, the results are descriptive of the subglottal respiratory system. These data characterize the neonatal respiratory system of infants with respiratory distress syndrome (with or without pulmonary interstitial emphysema) in the range of frequencies used during high frequency ventilation.
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Fenómenos Biomecánicos , Enfermedades del Recién Nacido/fisiopatología , Pletismografía Total/instrumentación , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Resistencia de las Vías Respiratorias , Humanos , Recién Nacido , Intubación Intratraqueal , Rendimiento Pulmonar , Oscilometría , Oxígeno/fisiología , Pletismografía Total/métodos , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/fisiopatología , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Parálisis Respiratoria/complicaciones , Parálisis Respiratoria/fisiopatologíaAsunto(s)
Fibrosis Quística/diagnóstico por imagen , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/diagnóstico por imagen , Hígado/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/patología , Humanos , Cirrosis Hepática Biliar/patología , MasculinoRESUMEN
Because oscillatory resistance of the respiratory system is often measured during tidal breathing, we studied the interaction between simultaneous oscillatory and unidirectional flows in three straight tubes (radius ranging from 0.3025 to 0.679 cm and length either 30.7 or 173 cm) and a central airway cast (tracheal radius 0.685 cm). Oscillatory flow was generated by a loudspeaker, airway pressure was measured with a transducer, and flow was calculated from pressure changes in an airtight enclosure mounted behind the flow source (loudspeaker plethysmograph). Oscillatory resistance, i.e., the real part of impedance, was determined from 2 to 64 Hz. In the absence of unidirectional flow, frequency dependence of resistance was observed for the two 30.7-cm-long tubes to match previously published theory. Frequency dependence of resistance for the airway cast was similar to that of the tube of comparable inlet radius. In the presence of unidirectional flow, oscillatory resistance at low frequency was independent of frequency and determined by the magnitude of the unidirectional flow. Oscillatory resistance at high frequency was frequency dependent but still influenced by the magnitude of the unidirectional flow. Our results indicate that the presence of unidirectional flow alters the oscillatory resistance of tubes and the cast at any given frequency, presumably by changing the shape of the boundary layer.
Asunto(s)
Ventilación Pulmonar , Resistencia de las Vías Respiratorias , Humanos , Métodos , Modelos Anatómicos , EspirometríaRESUMEN
We tested the hypothesis that features of upper airway and tracheal geometry can be inferred from acoustic reflection data recorded at the mouth. In six subjects we computed inferences of airway cross-sectional area vs. distance and compared them with measurements obtained from orthogonal radiographic projections of the trachea. The acoustic data show local area maxima at the uvula and hypopharynx and local minima at the oropharynx and the glottis. With subjects breathing air the inferred tracheal areas markedly exceeded the radiographic measurements. With subjects breathing 80% He-20% O2 there was good intrasubject agreement between acoustic and radiographic data in spite of large intersubject variability. The average coefficient of variation of tracheal area determinations for five trials in all subjects was 0.16. These studies suggest that features of airway geometry between the mouth and carina can be determined accurately and noninvasively in individual subjects from high-frequency reflection data measured at the mouth.