Infant lung function and tidal breathing patterns.
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Humans↗
Biomedical subjects
M Silverman
Publications and source records attributed to M Silverman.
Neonatal chronic lung disease and a family history of asthma.
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Asthma↗
Evaluation of the interrupter technique for measuring change in airway resistance in 5-year-old asthmatic children.
The interrupter technique is a noninvasive method for measuring airway resistance during quiet breathing which requires minimal subject cooperation. It, therefore, has enormous potential for use in young children unable to cooperate with conventional lung function tests. We evaluated the interrupter technique during bronchial challenge with methacholine administered by the tidal breathing method in 10 5-year-old asthmatic children. The mouth pressure/time [P mo(t)] curve obtained following brief airflow interruption during the expiratory phase of quiet breathing was analyzed to determine the interrupter resistance (Rint) using four different methods: RintC, a smooth curve fit with back-extrapolation; RintEO, calculated from the pressure change after the postinterruption oscillations had decayed (end-oscillation); RintL, two-point linear fit with back-extrapolation; and RintEI, calculated from the pressure change at the end of the period of interruption. The four Rint methods were compared for repeatability and sensitivity with the direct measurement of resistance by the forced oscillation technique (Rrs), and with an independent method of measuring the response to challenge, utilizing the change in transcutaneous oxygen tension (PtcO2). The sensitivity of the methods was defined by a sensitivity index (SI), the change after challenge expressed in multiples of the baseline standard deviation. The PtcO2 method had the lowest variability and was by far the most sensitive method (geometric mean SI 18.9), at least 1 doubling concentration more sensitive than the other techniques in every subject (P < 0.05). RintL was more sensitive than the other interrupter methods (geometric mean SI: RintL 4.2; RintC 1.0; RintEO 2.7; RintEI 3.1; P < 0.05) and similar in sensitivity to Rrs (geometric mean SI 4.6) in 7 out of 10 children in which this could be measured. We conclude that the interrupter method provides a simpler method than the oscillation technique for assessing airway obstruction in this age group.
Airway Resistance↗
Respiratory inductive plethysmography in the evaluation of lower airway obstruction during methacholine challenge in infants.
Respiratory inductive plethysmography (RIP) is a simple technique for an objective, noninvasive assessment of thoracoabdominal asynchrony, which in turn is an indirect measure of airway obstruction. We evaluated different indices of asynchrony obtained by RIP before and after methacholine-induced airway obstruction. Bronchial obstruction was elicited by progressive doubling concentrations of methacholine until a > 15% fall in the transcutaneous oxygen tension (PtcO2) had developed. Maximal expiratory flow rates at functional residual capacity (FRC) (VmaxFRC) was obtained by the squeeze technique before and after the challenge. Fifteen infants with a history of wheezing were studied after sedation. Thoracoabdominal movements were recorded with RIP bands placed around either the upper or the lower ribcage (RC) and around the abdomen (AB). An inspiratory asynchrony index (IAI) and an expiratory asynchrony index (EAI) were calculated as determined by the lag of RC relative to AB at start of inspiration and of expiration, respectively. The total time in asynchrony (TTA: the percentage of time in which the RC and the AB signals were in opposite direction) and phi (an angle derived from a Lissajous loop) were also calculated. All subjects responded to the challenge. The median fall in PtcO2 following methacholine challenge was 23.6% and in VmaxFRC was 43%. A large scatter of baseline values was found for all indices with the exception of TTA. There was no correlation between TTA and age, length, or VmaxFRC. The IAI and EAI with the RC band in the upper position were the most sensitive indices, both within subjects (65% of the subjects had a significant change in IAI and 80% in EAI) and for the group as a whole (median values increased for IAI, P = 0.007, and for EAI, P = 0.017). TTA and phi were less sensitive, and a great discrepancy was observed between the two measurements. Poor results were obtained with the RC band in the lower position. No correlations were found between the changes in IAI and EAI, with the RC band around the lower chest and VmaxFRC. We conclude that IAI and EAI, measured with the RC band in the upper position and another band around the abdomen, can detect changes in thoracoabdominal asynchrony in most infants. The usefulness of assessing IAI and EAI in infants with acute lower airway obstruction needs to be determined.
Abdomen↗
A new light-cured glass ionomer cement that bonds brackets to teeth without etching in the presence of saliva.
Previous studies stress certain advantages of glass ionomer cements, for use in bonding orthodontic brackets to teeth. Failure rate, however, had been higher than with conventional procedures. A new light-cured glass ionomer cement exhibited all the necessary qualities needed to bond brackets, without any etching and in the presence of saliva. The tensile strength of this cement exhibited enough resistance to forces needed to move teeth. The debonding procedures were also completely undamaging to the underlying enamel surfaces. On removal of the appliances, no decalcification was observed on any teeth, because the cement releases fluoride. Both the time saved during a routine strap-up, plus the ease to both the operator and the patient, could make light-cured glass ionomer cement the ultimate choice for bonding techniques after many trials, this cement is now being routinely and successfully used on all patients.
Acid Etching, Dental↗
Puromycin aminonucleoside inhibits mesangial cell-induced contraction of collagen gels by stimulating production of reactive oxygen species.
Glomerular epithelial cell injury is thought to be the primary reason for the development of proteinuria in puromycin aminonucleoside nephrosis (PAN), the rat model of nephrotic syndrome. By comparison mesangial cells are considered resistant to the effects of puromycin. The purpose of the present study was to investigate whether puromycin in non cytotoxic concentrations caused mesangial cell dysfunction, with particular reference to cell-extracellular matrix interactions. Mesangial cells, when embedded in collagen gels, contact after exposure to minimal essential medium (MEM) containing fetal bovine serum (FBS). This contractility, measured by determining changes in area of the collagen gel, is inhibited by puromycin in a dose dependent manner from 2.5 micrograms/ml to 160 micrograms/ml. At these concentrations there is no alteration of cell viability as measured by the tetrazolium salt (MTT) method and trypan blue exclusion. Immunocytochemistry with rhodamine phalloidin reveals that actin filaments are not disrupted. The antioxidants, superoxide dismutase (SOD) and catalase as well as diphenylene iodonium (DPI), a flavoprotein inhibitor, not only counteracted the effect of puromycin on gel contraction, but also enhanced gel contraction when added to mesangial cells on their own. Aminotriazole, an inhibitor of endogenous catalase, inhibited mesangial cell-induced gel contraction in a dose dependent manner (5 mM to 40 mM), and this effect was completely reversed by addition of catalase. Mesangial cells preloaded with dihydrorhodamine and exposed to puromycin (5 micrograms/ml to 160 micrograms/ml) exhibited a dose dependent increase in rhodamine 123 fluorescence, indicating production of reactive oxygen species (ROS). This effect was blocked by the addition of DPI.(ABSTRACT TRUNCATED AT 250 WORDS)
Amitrole↗
Evaluation of outpatient geriatric assessment: a randomized multi-site trial.
OBJECTIVE: To evaluate the process and outcome of outpatient consultative geriatric assessment compared with traditional community care. DESIGN: Randomized, controlled clinical trial, with 12-month follow-up. SETTING: Four hospital-based ambulatory geriatric assessment clinics and community physicians' offices. PARTICIPANTS: 442 recruited older adults with a health problem or recent change in health status. INTERVENTION: Outpatient consultative geriatric assessment or usual physician assessment. MAIN OUTCOME MEASURES: Identification of health problems, mortality, nursing home admissions, health status, health services utilization, satisfaction with care, and caregiver well-being. RESULTS: Geriatric assessment, in comparison with usual community care, resulted in the identification of a significantly greater number of patients with cognitive impairment (P < .0001), depression (P = .0004) and incontinence (P < .0001). The group receiving a geriatric assessment had greater improvement in anxiety levels at 1 year (P = .036). Caregivers of participants in the geriatric assessment group had less caregiver stress at 1 year (P = .002). No outcome differences in mortality, nursing home admissions, cognitive health, functional health, or health services utilization were observed. Some evidence of greater patient satisfaction with respect to qualities of the physician was found for the geriatric assessment group. CONCLUSIONS: Consultative outpatient geriatric assessment led to significantly improved diagnosis of the common health problems of cognitive impairment, depression, and incontinence, to psychological and emotional benefits for patients, and to reduced levels of caregiver stress. Even with limited follow-up care and control of treatment, outpatient geriatric assessment has potential for significant positive effects.
Aged↗
Effect of continuous treatment with topical corticosteroid on episodic viral wheeze in preschool children.
Acute episodic wheeze related to viral infections is a common and distressing condition and treatment remains unsatisfactory. Although some benefit from the continuous use of inhaled steroids has been demonstrated in young wheezy children, their effect primarily on acute episodes has not been considered. In this study the effect of budesonide (400 micrograms/day) was assessed in a four month double blind parallel trial, in 41 children (0.7-6.0 years) with predominantly episodic viral wheeze. Analysis of the last three months showed no difference between budesonide or placebo in mean daily total symptom score (median values 0.6 and 0.63), episode number (mean values 2.6 and 2.4), or score/episode (mean value 30 and 31). Four months of treatment with inhaled budesonide had no effect on acute episodes of wheeze in this group of children.
Acute Disease↗
Pulmonary hypertension in infants with chronic lung disease: non-invasive evaluation and short term effect of oxygen treatment.
A total of 45 examinations on 30 premature infants with chronic lung disease (CLD) of prematurity were made using Doppler echocardiography. Pulmonary systolic time intervals and tricuspid regurgitant velocity were measured to assess the prevalence of pulmonary hypertension and short term responsiveness of the pulmonary circulation to oxygen. Twelve preterm infants matched for gestational age, served as controls. Tricuspid regurgitation (TR) was detected in 14 of the patients. Eleven of those with TR had pulmonary hypertension, of whom eight responded to oxygen treatment. Of the remaining three patients with 'fixed' pulmonary hypertension, one subsequently died. The detection of TR was the basis of the preferred method for measuring pulmonary artery pressure (Ppa) non-invasively, but the degree of correlation between the Ppa estimated from TR and pulmonary systolic time intervals was high (r = -0.84, p = 0.001). In the absence of TR, systolic time intervals are an effective way to monitor pulmonary artery pressure in infants with CLD. Without these measurements, it would have been impossible to predict which subjects had pulmonary hypertension, and which might respond to oxygen treatment.
Blood Pressure↗
Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease.
Interleukin-8 (IL-8), soluble intercellular adhesion molecule-1 (sICAM), elastase and neutrophils were assessed in bronchoalveolar lavage fluid from nine infants who developed chronic lung disease (CLD) after respiratory distress syndrome (RDS), seven who had recovered from RDS, and in four control infants. IL-8, sICAM, elastase and neutrophils in bronchoalveolar lavage fluid were increased in the CLD group, the differences being most pronounced at 10 days of age. When babies with and without CLD were compared at 10 days of age, bronchoalveolar lavage fluid from the babies with CLD had significantly increased IL-8 (114.0 vs 12.7 ng/ml), sICAM (19.0 vs 1.1 micrograms/ml), elastase (6.9 vs 0.9 micrograms/ml) and neutrophils (1.9 vs 0.4 x 10(9)/l). In serum the increased concentration of IL-8 observed at birth in the CLD (247 pg/ml) and RDS (192 pg/ml) groups decreased over three weeks to the concentrations observed in the controls (< 70 pg/ml). Persistent inflammation could be a major contributory factor in the development of CLD.
Bronchoalveolar Lavage Fluid↗
Antioxidants in neonatal lung disease.
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Antioxidants↗
Bronchial responsiveness and symptoms in 5-6 year old children: a comparison of a direct and indirect challenge.
BACKGROUND: The level of bronchial responsiveness in those with definite asthma correlates with disease severity and markers of airway inflammation. However, in population studies no clear distinction between normal and abnormal is found. Since the outcome of wheeze in early childhood is very variable, a marker of underlying airway inflammation would be of practical value. A stimulus acting indirectly may be more appropriate than one acting directly on smooth muscle. In this study the airway response to a direct (methacholine) and indirect (hypertonic saline) challenge have been compared in 5-6 year old children with past or present wheeze to see if symptom patterns or severity could be distinguished by either test. METHODS: Forty children with a wide spectrum of wheeze were monitored for a six month period after which their pattern and severity of symptoms were graded. Hypertonic saline and methacholine challenges were then performed on separate days. The response was assessed by both respiratory resistance (Rrs6) and transcutaneous oxygen (PTCO2). Atopic status was determined by IgE and skin prick tests. RESULTS: The results of both challenges were similar whether assessed by Rrs6 or PTCO2. There was no difference in the response to either methacholine or saline between different symptom patterns or severity grades, nor was there any correlation with either test to atopic status. CONCLUSIONS: Neither an indirect nor a direct challenge distinguished between past or present wheeze or degree of clinical severity in this group of children. Either wheezy children of this age do not have airway inflammation or bronchial responsiveness is not a marker for it.
Asthma↗
Comparison of four methods of assessing airflow resistance before and after induced airway narrowing in normal subjects.
Four methods for assessing airflow resistance were compared in seven normal adults at baseline and after inducing airway narrowing with inhaled methacholine. Airway resistance (Raw) was measured during panting at 1-2 Hz within a body plethysmograph; total lung resistance was measured by using an esophageal balloon during quiet breathing (RLq) and with doubling of frequency while maintaining the original tidal volume; total respiratory resistance (Rrs) was measured at 6 Hz during forced oscillation applied at the airway opening, and interruption resistance (Rint) was measured at midtidal expiratory flow. Three methods of obtaining Rint after airflow interruption were compared [smooth curve fit of mouth pressure (Pm) back extrapolated to valve closure; two-point linear fit of Pm back extrapolated to 15 ms after closure; and Pm at 100 ms after valve closure]. We found similar basal median values (cmH2O.l-1.s) of Raw (1.3), RLq (1.4), RL of double resting frequency (1.9), Rrs (1.7), and smooth curve fit of Pm back extrapolated to valve closure (1.5); basal values of two-point linear fit of Pm back extrapolated to 15 ms after closure (2.4) and Pm at 100 ms after valve closure (4.4) were considerably larger. After induced airway narrowing, all methods of measuring resistance showed significant increases; these were largest with RLq (median %change of 265) and smallest with the three Rint methods (median %change of 62-72). Rint and Rrs methods had poorer sensitivity for detecting bronchoconstriction than lung resistance of Raw. Of the Rint methods, end interruption pressure was the most sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Bronchial responsiveness in the neonatal period as a risk factor for wheezing in infancy.
Bronchial responsiveness is closely associated with asthma in schoolchildren. We wished to test the hypothesis that bronchial responsiveness in the neonatal period might be a risk factor for lower-respiratory illnesses (LRI), typically cough and wheezing with viral infection, in infants. A cohort of 73 full-term healthy infants of atopic parents were observed during the first year of life. Respiratory illness was recorded and ascertained retrospectively by questionnaires administered to parents at 6-mo intervals, and infants were classified as having: LRI (one or more episode of wheezing in the first year) or no LRI (no wheezing). At approximately 1 mo of age, lung function was measured under sedation, and bronchial responsiveness (BR) to histamine aerosol was determined and expressed as PC30, the provocative concentration of histamine that induced a 30% decrease in maximum flow at FRC (V'maxFRC) by the squeeze technique. For the whole group, no index of lung function predicted subsequent wheezing. Among boys, however, there was a trend toward a lower V'maxFRC in those who subsequently developed LRI than in the group without LRI (median values 62 versus 98 ml/s; 95% CI: -1 to 68; p = 0.06), while among girls the major difference was in PC30, for which those who subsequently had LRI were significantly more responsive as neonates (PC30 was lower) than the group without LRI (1.4 versus 8.3 g/L; 95% CI: 1.0 to 13.1; p < 0.05). These findings suggest that sex differences in airway structure and responsiveness present soon after birth, and representing differences in fetal lung development, are associated with differences in the risk of subsequent LRI with wheezing.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchial Hyperreactivity↗
The measurement of methacholine responsiveness in 5 year old children: three methods compared.
The aim of this study was to compare the feasibility of three techniques for measuring the response to bronchial challenge in young children: a direct airway measurement, the forced oscillation technique (FOT) for determining respiratory system resistance at 6 and 8 Hz (Rrs6 and Rrs8), and two indirect methods, the change in transcutaneous oxygen tension (PtcO2) and the detection of wheeze on auscultation of the chest. Thirty children aged 5 yrs, with a history of wheeze, and six asymptomatic controls, took part in a bronchial challenge test using methacholine administered by Wright nebulizer by the tidal-breathing method. The provocative concentration which produced a 35% increase in Rrs6 (PC35Rrs6) and a 15% decreases in PtcO2 (PC15PtcO2) were determined by interpolation, and the chest was ausculated after each dose of methacholine. The FOT was found to be unreliable in this age group: in seven children, the data were technically unsatisfactory in the presence of induced bronchoconstriction, whilst in three children, changes in Rrs were inconsistent after challenge. The use of Rrs8 did not improve the detection of positive responses. PC15PtcO2 was measurable in 29 of 30 children, and in 18 of these PC35Rrs6 was also measurable. In no subject did a significant, sustained increase in Rrs occur during challenge in the absence of a significant change in PtcO2. Wheeze was audible in only 4 of 25 (16%) of the positive and in no negative challenges. With this protocol, we found the FOT to be unreliable and the auscultation method valueless and potentially dangerous, since marked falls in PtcO2 of up to 33% sometimes occurred in the absence of wheeze.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway Resistance↗
Transmembrane aromatic amino acid distribution in P-glycoprotein. A functional role in broad substrate specificity.
Multidrug resistance (MDR) in cancer cells is associated with overexpression of P-glycoprotein (Pgp), a membrane protein which interacts with structurally diverse hydrophobic molecules of high membrane affinity. In an analysis of the molecular basis for this broad range of substrate specificity, we found that the transmembrane (TM) regions of Pgp are rich in highly conserved aromatic amino acid residues. Computer-generated three-dimensional model structures showed that a typical substrate, rhodamine 123, can intercalate between three to four phenylalanine side-chains in any of several Pgp TM helices with minimal protrusion of the drug into bulk lipid, and that five to six (of the 12 Pgp putative TM segments) helices can facilitate transport through creation of a sterically compatible pore. In contrast to the case for proteins involved in the transport of membrane-impermeable, relatively polar substrates, the "transport path" for Pgp substrates need not be polar, and may involve either an internal channel occupied largely by aromatic side-chains, or external gaps along TM helix-lipid interfaces. Weakly polar interactions between drug cationic sites and Pgp aromatic residues contribute additionally to overall protein/drug binding. The ability of Pgp to recognize and efflux structurally diverse molecules suggests that rather than a unique structure, the Pgp channel may maintain the intrinsic capacity to undergo wide-ranging drug-dependent dynamic reorganization.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Are tidal breathing indices useful in infant bronchial challenge tests?
Tidal breathing indices have been used to assess histamine-induced airway obstruction in adults and children. The aim of this study was to see whether they could be used to assess histamine challenge in infants. Tidal flow during quiet breathing was measured using a face mask and pneumotachograph and maximum flow at functional residual capacity (VmaxFRC) was measured from partial forced expirations in 18 sleeping, sedated infants who responded to histamine challenge and in 18 nonresponders. The tidal indices calculated were inspiratory and expiratory time (ti and te), tidal peak expiratory flow (PEF), mean tidal expiratory flow rate (VT/te) and the expiratory time constant of the respiratory system (trs). The time to maximal expiration divided by expiratory time (tme/te) and 2 revised forms of this index (tme(a)/te and tme(b)/te) were also calculated. Recordings of tme(a) and tme(b) were taken at 95% of peak tidal expiratory flow, before and after the peak, respectively. In nonresponders, there was an insignificant mean rise in VmaxFRC of 11.8% but no change in any tidal index. In responders, the mean percentage fall in VmaxFRC was 43.3% (range, -31 to -81%); trs fell from 0.61 s to 0.51 s (P < 0.05) and breathing frequency and mean tidal expiratory flow rate increased from 34.0 to 37.5 min-1 (P < 0.01) and from 66.6 to 72.6 mL.s-1 (P < 0.05), respectively, suggesting that infants had adopted a strategy of active expiration in response to bronchial challenge. There was no change either in tme/te or in the revised indices after challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Evaluation of a tidal expiratory flow index in healthy and diseased infants.
Patterns of tidal respiratory flow have been shown to relate well to airway function in adults, and one epidemiological study in infants has demonstrated the value of the ratio of time to reach peak tidal expiratory flow to the total expiratory time (tpef/te) in predicting subsequent wheezing. The aim of this study was to evaluate tpef/te as a measure of lung function, by sequential observations over the first year, on a group of 22 healthy infants and on 32 infants with a history of mild recurrent lower respiratory illness (LRI), and by single observations on 20 infants with asthma and 20 with severe chronic lung disease of prematurity. We compared tpef/te measured in quiet, supine sleep (under sedation) through a face mask and pneumotachograph, with a measure of airway function, maximal flow at functional residual capacity (VmaxFRC), obtained from partial forced expiratory flow volume loops using the "squeeze" technique. In healty infants tpet/te was significantly longer at 1 month than at 6 months (median values, 0.38 (95% CI, 0.36-0.43) and 0.28 (95% CI, 0.26-0.33), respectively). Between 6 and 12 months tpef/te did not alter significantly and it was independent of VmaxFRC. Both tpef and te as well as their ratio varied with frequency of breathing over the first year of life, but not within each individual age band, due to the narrow spread of frequencies at each age. In assessing airway obstruction, tpef/te was less sensitive than VmaxFRC. There was no difference between healthy infants, those with LRI, and infants with asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗