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Significance Although resistance to glucocorticoids is a major clinical problem, the underlying mechanisms are unknown. It is known that glucocorticoid use can suppress adrenal androgen production. In population studies, animal models, and cell culture experiments, androgens are associated with several benefits in asthma, but neither androgen use in glucocorticoid-resistant asthma nor the genetic determinants of androgen responsiveness have been studied in humans. A missense-encoding variant in HSD3B1 is known to regulate conversion from adrenal precursors to potent androgens and clinical outcomes in prostate cancer. This is the first genetic evidence to our knowledge that implicates an androgen synthesis variant in resistance to glucocorticoids for asthma or any other inflammatory disease. Furthermore, this study demonstrates an adverse consequence of adrenal androgen suppression with glucocorticoid therapy., Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention.

To characterize a cohort of children with airflow limitation resistant to bronchodilator (BD) therapy.Pulmonary function tests performed in children 6-17 years of age at 15 centers in a clinical research consortium were screened for resistant airflow limitation, defined as a post-BD FEV582 children were identified. Median age was 13 years (IQR: 11, 16), 60% were males; 62% were Caucasian, 28% were African-American; 19% were obese; 32% were born prematurely and 21% exposed to second hand smoke. Pulmonary diagnoses included asthma (93%), prior significant pneumonia (28%), and bronchiectasis (5%). 65% reported allergic rhinitis, and 11% chronic sinusitis. Subjects without a history of asthma had significantly lower post-BD FEVThe most prevalent diagnosis in children with BD-resistant airflow limitation is asthma. Allergic rhinitis and premature birth are common co-morbidities. Children without a history of asthma, as well as those with asthma but no allergic rhinitis, had lower pulmonary function. Children with BD-resistant airflow limitation may represent a sub-group of children with persistent obstruction and high risk for life-long airway disease.

Background Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP). Methods We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1 ). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility. Results We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1 % predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1 % predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility. Conclusions Lung function, that is FEV1 % predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.

© 2019 Asian Pacific Society of Respirology Background and objective: The reduction of forced expiratory volume in 1 s (FEV1) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV1/forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC). Methods: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV1, and calculated as %ΔFVC/%ΔFEV1. Results: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control. Conclusion: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.

Identification of risk factors for reduced asthma control could improve the understanding and treatment of asthma. A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy, but its impact on disease control remains unclear.We sought to determine if the ALOX5 promoter SP1 tandem repeat polymorphism was associated with changes in cysteinyl leukotriene production, lung function, airway inflammation and asthma control score.We analysed 270 children, 6- to 17-years old, with poorly controlled asthma enrolled in a 6-month clinical trial (NCT00604851). In secondary analysis, we associated the ALOX5 promoter SP1 tandem repeat polymorphism genotype (rs59439148) with asthma outcomes using both additive and recessive genetic models. We evaluated FEV1 percent predicted, symptom control, exhaled nitric oxide and urinary LTE4 levels.Of all children, 14.8% (40/270) (and 28% (38/135) of African Americans) carried two non-5-repeat variant alleles of rs59439148. Children who were homozygous for variant alleles had significantly higher urinary LTE4 levels (38 vs. 30 nmol/mol creatinine, P = 0.0134), significantly worse FEV1% predicted (84 vs. 91, P = 0.017) and a trend towards worse asthma control. FEV1% predicted values were significantly negatively correlated with urinary LTE4 (r = -0.192, P = 0.009).Carrying two copies of a minor variant ALOX5 promoter SP1 tandem repeat allele contributes to increased cysLT exposure as determined by urinary LTE4 levels, reduced lung function and potentially worse asthma control. ALOX5 promoter SP1 tandem repeat genotype may be a risk factor for worse asthma outcomes.

The childhood Asthma-Control Test (C-ACT) is validated for assessing asthma control in paediatric asthma. Among children aged 4–11 years, the C-ACT requires the simultaneous presence of both parent and child. There is an unmet need for a tool that can be used to assess asthma control in children when parents or caregivers are not present such as in the school setting. We assessed the psychometric properties and estimated the minimally important difference (MID) of the C-ACT and a modified version, comprising only the child responses (C-ACTc). Asthma patients aged 6–11 years (n=161) from a previously completed multicenter randomised trial were included. Demographic information, spirometry and questionnaire scores were obtained at baseline and during follow-up. Participants or their guardians kept a daily asthma diary. Internal consistency reliabilities of the C-ACT and C-ACTc were 0.76 and 0.67 (Cronbach’s α), respectively. Test–retest reliabilities of the C-ACT and C-ACTc were 0.72 and 0.66 (intra-class correlation), respectively. Significant correlations were noted between C-ACT scores and ACQ scores (Spearman’s correlation r=−0.56, 95% CI (−0.66, −0.44), P

Introduction Critically ill children treated with extracorporeal membrane oxygenation (ECMO) support frequently have respiratory complications amenable to evaluation by flexible bronchoscopy (FB). The safety and efficacy of FB in this setting has not been well described in children. Methods Retrospective analysis of 153 FBs in 79 children treated with ECMO at a single institution from 2000 to 2008. Demographic data, clinical findings, and complications were obtained. Chest radiographs reports were evaluated prior to and following FB. Physiologic variables were compared prior to and following FB. Results Seventy-nine patients underwent FB on ECMO [58 veno-venous (VV) and 21 veno-arterial (VA) ECMO], with 153 total FBs performed. Indications for FB included clearance of tenacious airway secretions (n = 118, 77%), or evaluation of suspected secondary infections with bronchoalveolar lavage (n = 26, 17%). Two patients also had surfactant instillation following secretion removal. FB was performed a median 5 days following cannulation for ECMO (range 2–14 days). Most common findings included thick secretions (n = 77, 50.3%), mucoid secretions (n = 15, 9.8%), and mucopurulent secretions (n = 28, 18.3%). No deterioration in radiographic lung findings was described post-FB. FB was not associated with any significant change in heart rate, systemic blood pressure, or temperature. No significant changes in ECMO pump flow rate or sweep gas flow was seen during or after FB. Cannula dislodgement, inadvertent extubation, fever, pneumothorax, or intraprocedural hypoxemia was not reported. Fifty-three FBs (35%) resulted in blood-tinged secretions from the endotracheal tube post-FB, which resolved spontaneously. Three patients received high frequency oscillatory ventilation (HFOV) following FB in association with mild hemorrhage. Conclusions FB is a well-tolerated and safe procedure in critically ill pediatric patients on ECMO. FB may have a diagnostic as well as therapeutic benefit in such patients. Pediatr. Pulmonol. 2011; 46:1108–1113. © 2011 Wiley Periodicals, Inc.

Asthma exacerbations are associated with decreased quality of life and increased health care usage. Identification of characteristics that predict increased risk of future exacerbations in patients with suboptimal control of asthma could guide treatment decisions.To examine patient characteristics associated with risk of asthma exacerbations in patients with uncontrolled persistent asthma.A retrospective analysis of adults and children with inadequately controlled asthma despite asthma controller therapy and enrolled in 2 randomized trials was conducted. Baseline characteristics of subjects who experienced an asthma exacerbation during the treatment period were compared with those of subjects who did not experience an exacerbation.Of 718 subjects (402 adults and 295 children), 108 adults (27%) and 110 children (37%) experienced an asthma exacerbation during the study period. Unscheduled health care visits for asthma or use of oral corticosteroids in the previous year were significantly associated with asthma exacerbation during the study period (P.01). Adult subjects who experienced an exacerbation had significantly lower forced expiratory volume in 1 second compared with those who did not (2.3 vs 2.5 L, respectively, P = .02). Children who experienced an exacerbation had lower baseline pre- and post-bronchodilator ratios of forced expiratory volume in 1 second to forced vital capacity (77% vs 81%, P.01; 82% vs 86%, P.001, respectively). Symptom scores on validated questionnaires were significantly worse in adults but not in children who developed an exacerbation.Spirometric measurements can help identify adults and children at increased risk for asthma exacerbation. Symptom scores could be helpful in identifying adults who are at high risk for exacerbations but could be less helpful in children.

Objective To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. Study design Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. Results The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02-5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86-2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23-7.05, P = .016) vs 1.97 (1.09-3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). Conclusions Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.

Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157).The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.clinicaltrials.gov Identifier: NCT00442013.

Background The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining "exacerbation" or about how to characterize an episode's severity. Objective National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies. Methods We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health–organized workshop in March 2010 and finalized in September 2011. Results No dominant definition of "exacerbation" was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting β-agonists as quick-relief (sometimes referred to as "rescue" or "reliever") medications. Conclusions The working group participants propose that the definition of "asthma exacerbation" be "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome." As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of "exacerbation" with clear thresholds of severity for each component.

Severe asthma in children is a complicated disorder characterized by ongoing symptoms and persistent airway inflammation despite treatment with high doses of inhaled and oral corticosteroids. Although knowledge of asthma and its associated mechanisms has increased substantially over the past decade, significant gaps remain about the determinants of severe asthma in children and the progression of the disorder across the lifespan. This review highlights recent insights into severe asthma in children derived from the National Heart, Lung, and Blood Institute's Severe Asthma Research Program (SARP), with an emphasis on age-specific findings and differences from severe asthma in adults. While the existence of a true severe asthma phenotype in children is subject to some debate, given the results of SARP and other investigators, we conclude that there is indeed a subgroup of children with severe asthma who have extreme morbidity and differentiating clinical features that are identifiable very early in life. However, unlike adults with severe asthma, children with severe asthma are more likely to fall in a more narrow cluster that is characterized by marked atopy and reversible airflow obstruction. While SARP has advanced knowledge of severe asthma in children, considerable gaps remain for which additional studies are needed.

Despite governmental efforts to improve the quality of outdoor air, a significant number of children growing up in the US are exposed to airborne pollutants. It is now recognized that infants generally at risk for atrophy when exposed to specific environmental airborne pollutants are more likely to develop asthma. Once asthma is established, airborne pollutants are important triggers in causing exacerbations. Airborne ozone and suspended articles are the two most important criteria pollutants with respect to exposure prevalence and suspected adverse health effects in US children. Pediatricians should be involved both in community advocacy programs to improve air quality and as knowledgeable practitioners in discussing practical air pollution avoidance strategies with patients and their families.

Hypoxia causes the release of atrial natriuretic factor (ANF), but the mechanisms are not yet understood. This study examined the relative contribution of pulmonary arterial hypertension, neural pathways, increased heart rate, or increased atrial size to the ANF response. Alveolar hypoxia [fractional concentration of O2 in inspired gas (FIo2) = 0.1] or pulmonary arterial hypertension (25-45 mmHg) was induced for 10 min in four series (n = 4-12 each) of anesthetized, mechanically ventilated pigs. During hypoxia, plasma ANF concentrations increased by 129 +/- 52 (SE) pg/ml (or 271 +/- 105%) over baseline (35 +/- 7 pg/ml; P less than 0.01) (series 1). There was also a significant increase of pulmonary arterial pressure, heart rate, central venous pressure, and pulmonary capillary wedge pressure. Repeated pulmonary hypertension induced by intravenous air infusion caused a repeated and reversible 125 +/- 14% increase (P less than 0.001) of plasma ANF, and this response was totally abolished by lesion of the cervical vagosympathetic trunks (series 2). Lesion of these nerves 1 h before hypoxia also decreased the ANF response to hypoxia by 45-58% (P less than 0.01), whereas responses of heart rate and atrial pressures were unchanged (series 3). The ANF response to hypoxia, expressed in percent of baseline, was not affected by 0.2 mg/kg propranolol (PR) (no PR: 145 +/- 63%; PR: 151 +/- 82%; not significantly different from series 1 and control, series 3), although the increase in heart rate (no PR: 61 +/- 15 beats/min) was almost abolished (PR: 17 +/- 5 beats/min) (series 4). Hypoxia caused no significant changes in right and left atrial peak volume regardless of propranolol, as measured with an electrical conductance catheter. The results indicate that a new neural reflex of probably pulmonary arterial origin mediates approximately 50% of the ANF response to hypoxia. The remaining ANF response remains to be explored further and cannot be explained by conventional release mechanisms such as atrial stretch and pulsatility alone.

The constant-flow properties of time-cycled ventilators can be used to measure infant respiratory mechanics. We used a pulse method that does not interrupt inflationary flow to measure lung compliance (Cl) and respiratory system compliance (Crs) of 16 infants who required assisted ventilation. When the infants were relaxed, constant-flow inflation produced transrespiratory pressure tracings with constant slope segments. We calculated pulse Crs from inflationary flow divided by the slope of the pressure tracing, and compared the results to static and dynamic Crs values determined by standard methods. The pulse method accurately measured static Crs (r = .93) with a low intrasubject coefficient of variation (3.4%). Pulse and static Crs values consistently exceeded dynamic Crs (p less than .005). Cl measured with each method exceeded Crs (p less than .05), but the magnitude was clinically unimportant. Pulse Crs is a noninvasive measurement of static respiratory system recoil which proved to be sensitive to changes in respiratory muscle tone.

Bronchiolitis obliterans (irreversible small airway obstruction) is a late complication of heart-lung transplantation. Chronic immune rejection is believed to be the major cause of this complication. Our hypothesis was that denervation might contribute to airway obstruction. To test this hypothesis in the absence of immune rejection, we performed a lobectomy of the upper lobe of the left lung and autologous reimplantation of the lower lobe of the left lung in 13 growing pigs. To serve as age-matched controls, six other pigs had sham left thoracotomy and nine others had a lobectomy of the upper lobe of the left lung alone. Nine to 10 weeks after operation, the animals were anesthetized and the lungs mechanically ventilated. The lobes were then isolated in vivo to measure differential transrespiratory mechanics and volumes. Dynamic compliance was significantly lower in the reimplanted lobe than it was in the contralateral right lung. This was the case after lobectomy of the upper lobe of the left lung or sham thoracotomy. Dynamic resistance was significantly higher in the reimplanted lobe than it was in the contralateral right lung and in the left lung after sham thoracotomy. Measurements of extravascular lung water, dry lobe weight, alveolar cross-sectional area, and volumetric proportions of lung parenchyma and alveolar spaces did not demonstrate abnormal structural growth after reimplantation. We conclude that lobectomy of the upper lobe of the left lung and autologous reimplantation of the left lower lobe leads to adverse changes in flow-dependent measurements of airway patency. Changes in bronchomotor regulation imposed by denervation may contribute to airway obstruction after heart-lung transplantation.

The effect of acute alveolar hypoxia [fractional concentration of O2 in inspired gas (FIo2) = 0.1] for 10 min [arterial PO2 = 37 +/- 4 (SE) mmHg] and of blood volume expansion (7 and 15% of calculated blood volume) on atrial natriuretic factor (ANF) release was examined in groups of awake, instrumented young lambs. Systemic venous plasma ANF concentrations increased 1.6-fold (P less than 0.01) during blood volume expansion of 7%, 1.9-fold (P less than 0.01) during acute hypoxia, and 2.2-fold (P less than 0.005) during blood volume expansion of 15%. In lambs with prior 15% blood volume expansion, alveolar hypoxia further increased ANF concentrations 3.1-fold (P less than 0.01), suggesting synergism between volume and hypoxia stimuli. Hypoxia-induced ANF release correlated best with increased pulmonary arterial pressure, a potential mediator of the ANF response (r = 0.67; P less than 0.016). Increased differences between pulmonary arterial and systemic venous plasma ANF concentrations (from 11 to 134 pg/ml) indicate that hypoxia causes increased release of ANF from the heart rather than decreased metabolism of circulating ANF. Pulmonary arterial plasma ANF during hypervolemic hypoxia had immunological and chromatographic (high-performance liquid chromatography) properties of Pro-ANF-(99-126) [alpha-ANF-(1-28)]. Thus alveolar hypoxia (FIo2 = 0.1) is as potent as 15% blood volume expansion in increasing the concentration of circulating ANF. This newly described endocrine response could be important during alveolar hypoxia to decrease pulmonary vasoconstriction and fluid accumulation in the lung.

Positive end-expiratory pressure (PEEP) decreases dynamic respiratory system compliance (Crs) in ventilated infants. As dynamic Crs measurements reflect airway resistance, we utilized a pulse method (J. Appl Physiol. 49:1116) to test the effect of PEEP on static Crs. We measured Crs in 11 infants (gestational age 33±4{mean±S.D.}weeks, weight 2052±704 gms, and study age 29±35 days) with respiratory failure supported with a constant flow ventilator. Flow, transrespiratory pressure, and tidal volume were recorded. We calculated pulse Crs by dividing flow by the slope of the linear portion of the pressure tracing. Static and dynamic Crs were measured by standard methods. Values of Crs were compared from PEEPs of 2.5 to 10.0 cms H2O. At the baseline ventilator settings, pulse and static Crs were similar (b=0.94, r2=90%), and both exceeded dynamic Crs (p