RESUMEN

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of under-ventilated lung units (UVLU). Additionally, we used 2 previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P<0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249ml [95%CI -10796; 580ml] and -203ml [95%CI -997;591ml], respectively). Parameters from both spirometry and body plethysmography were sub-optimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared to the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.

RESUMEN

RATIONALE: Imbalance between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (dysanapsis) has been reported in children who are obese. This dysanaptic growth might begin at an early age, although there are no data on children younger than 6 years. OBJETIVES: To assess whether body mass index (BMI) and early weight gain, in healthy infants born at term, plays a significant role in the imbalance between FEV1 and FVC, even in the absence of obesity. METHODS: Lung function was measured by means of raised volume rapid thoracic compression in 69 healthy infants born at term from the Nutrition in Early Life and Asthma cohort. Dysanapsis was defined as zFVC >0.674, zFEV0 .5 ≥-1.645, and FEV0 .5/FVC ≤-1.645. Weight gain (g/day) and growth rate (cm/year) were calculated as the difference between weight and length on the test date and those at birth. To assess the relationship between zBMI and dysanapsis, a receiver operating characteristic curve was performed. Multivariable analysis was carried out by means of linear regressions (one for each lung function index) and by logistic regression for dysanapsis (yes/no). RESULTS: Higher zBMI was associated with risk of dysanapsis (odds ratio: 3.53, [95% confidence interval: 1.30; 9.66]; p = .014): Each additional zBMI unit was associated with ~10 mL higher FVC and with ~3.5% lower FEV0.5/FVC. Weight gain was associated with lower FEV0.5/FVC ratio. CONCLUSION: Dysanaptic development of lung function begins very early in infancy and is related with weight gain and body mass index, even in the absence of obesity.

RESUMEN

BACKGROUND: Elexacaftor in combination with Tezacaftor and Ivacaftor (ETI) became licensed in the United Kingdom in early 2022 for children aged 6-11 years with cystic fibrosis (CF) and an eligible mutation. Many in this age group have excellent prior lung health making quantitative measurement of benefit challenging. Clinical trials purport that lung clearance index (LCI2.5) measurement is most suitable for this purpose. OBJECTIVES: This study aimed to understand the clinical utility of LCI2.5 in detecting change after commencing ETI in the real world. PATIENT SELECTION/METHODS: Baseline anthropometric data were collected along with spirometry (forced expiratory volume in 1 s [FEV1], forced vital capacityFV and LCI2.5 measures in children aged 6-11 years with CF before starting ETI. Measures were repeated after a mean (range) of 8.2 (7-14) months of ETI treatment. The primary endpoint was a change in LCI2.5, with secondary endpoints including change in FEV1 and change in body mass index (BMI) also reported. RESULTS: Twelve children were studied (seven male, mean age 9.5 years at baseline). Our study population had a mean (SD) LCI2.5 of 7.01 (1.14) and FEV1 of 96 (13) %predicted at baseline. Mean (95% confidence interval) changes in LCI2.5 [-0.7 (-1.4, 0), p = .06] and BMI [+0.7 (+0.1, +1.3), p = .03] were observed, along with changes in FEV1 of +3.1 (-1.9, +8.1) %predicted. CONCLUSIONS: Real-world changes in LCI2.5 (-0.7) are different to those reported in clinical trials (-2.29). Lower baseline LCI2.5 as a result of prior modulator exposure, high baseline lung health, and new LCI2.5 software analyses all contribute to lower LCI2.5 values being recorded in the real world of children with CF.

Asunto(s)

RESUMEN

Background: Chronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD. Methods: Of 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD. Results: Multivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p < 0.05); no association was found for variance in %predicted FEV1. Conclusion: Oscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.

RESUMEN

Since the beginning of the COVID-19 pandemic, multisystem inflammatory syndrome in children (MIS-C) has been reported in increasing numbers, mostly focusing on cardiac dysfunction. Very few studies have evaluated lung involvement in terms of imaging findings, while data regarding pulmonary function in children with MIS-C are not available. The purpose of our study was to evaluate lung involvement in MIS-C by imaging and lung function by structured light plethysmography (SLP) at hospital admission and 6 months afterwards. Spirometry is the gold standard technique to evaluate lung function in children. However, SLP has the advantage of not requiring contact with the patient, offering an effective solution for the evaluation of lung function during the pandemic. To our knowledge this is the first study that aims to investigate pulmonary function by SLP in children with MIS-C.

Asunto(s)

RESUMEN

Recently, a cross-talk error with commercial multiple breath nitrogen washout (MBWN2 ) software was discovered, which produced an absolute over-reading of N2 of approximately 1%, i.e., 2% N2 read as 3%. This caused an extended tail to the washout, and over-estimated lung clearance index (LCI2.5 ) values. Subsequently an updated and corrected software version has been released. Within the field there have been discussions on how to correct legacy data, whether to migrate or completely "rerun" raw data A-files from the old software into the new corrected software. To our knowledge, no research has been published assessing whether either method is equivalent to directly collecting data in the new corrected software. We prospectively recruited 19 participants, 10 adult healthy controls and 9 people with cystic fibrosis (CF). MBWN2 was performed using the Exhalyzer® D first on the old 3.1.6 software and next, directly on corrected 3.3.1 software. Multiple breath washout (MBW) data directly collected in 3.3.1 was significantly different from both migrated and rerun data. A total of 7 of the 19 participants (37%; 4 CF) had a relative difference in LCI2.5 > 10% for both migrated and rerun data compared to 3.3.1 collected data. Our findings have implications for the Global Lung Initiative MBW project, which is accepting a combination of directly collected, A-file reruns and migrated data to establish normative values. Further, caution must be used in clinical practice when comparing corrected legacy data versus 3.3.1 collected data for clinical interpretation. We recommend that a new baseline is collected directly on 3.3.1. before clinical interpretation and decisions are determined when comparing consecutive MBW tests.

Asunto(s)

RESUMEN

BACKGROUND: Adding a slow vital capacity (SVC) to multiple breath washout (MBW) allows quantification of otherwise overlooked signal from under/un-ventilated lung units (UVLU) and may provide a more comprehensive assessment of airway disease than conventional lung clearance index (LCI2.5). METHODS: We conducted a pilot study on people undergoing MBW tests: 10 healthy controls (HC) and 43 cystic fibrosis (CF) subjects performed an SVC after the standard end of test. We term the new outcome LCI with Short extension (LCIShX). We assessed (i) CF/ HC differences, (ii) variability (iii) effect of pulmonary exacerbation (PEx)/treatment and (iv) relationship with CF computed tomography (CFCT) scores. RESULTS: HC/ CF group differences were larger with LCIShX than LCI2.5 (P<0.001). Within the CF group UVLU was highly variable and when abnormal it did not correlate with corresponding LCI2.5. Signal showed little variability during clinical stability (n = 11 CF; 2 visits; median inter-test variability 2.6% LCIShX, 2.5% LCI2.5). PEx signal was significantly greater for LCIShX both for onset and resolution. Both MBW parameters correlated significantly with total lung CT scores and hyperinflation but only LCIShX correlated with mucus plugging. CONCLUSIONS: UVLU captured within the LCIShX varies between individuals; the lack of relationship with LCI2.5 demonstrates that new, additional information is being captured. LCIShX repeatability during clinical stability combined with its larger signal around episodes of PEx may lend it superior sensitivity as an outcome measure. Further studies will build on this pilot data to fully establish its utility in monitoring disease status.

Asunto(s)

RESUMEN

Inhaled bronchodilators are often given in preterm infants with evolving or established bronchopulmonary dysplasia. However, it is unclear which patients may benefit from it and when it is the best time to start treatment. The forced oscillation technique (FOT) is a noninvasive method for assessing lung mechanics that proved sensitive to airway obstruction reversibility in children and adults. FOT does not need patient cooperation, which is ideal for infants. Bedside tools for applying FOT in infants during spontaneous breathing and different respiratory support modes are becoming available. This case report illustrates for the first time that FOT has potential value in assessing airway obstruction reversibility in preterm infants, informing which infants may manifest a clinical benefit from the treatment with bronchodilators.

Asunto(s)

RESUMEN

BACKGROUND: Cystic fibrosis (CF) pulmonary exacerbations (PEx) are associated with a significant drop in pulmonary function. The clinical value of measuring bronchodilator (BD) responsiveness during treatment for PEx to monitor or predict recovery of lung function is unclear. METHODS: A retrospective analysis of spirometry with BD response testing obtained during hospital admissions for PEx in pediatric CF patients. Repeated events were included for patients with BD testing during multiple admissions. RESULTS: Two hundred forty-nine spirometries with BD testing in 102 patients were completed around Day 7 (Days 4-10) of hospital admission for treatment of CF PEx. Median (IQR) forced expiratory volume in 1 s (FEV1 ) was 70.6% predicted (58.1, 84.6) before the PEx event (best FEV1 in 6 months before admission), 54.4% (41.5, 66.9) at admission, 62.3% (48.4, 74.7) around Day 7 of admission and 67.1% predicted (53.8, 78.2) at the end of treatment. BD response around Day 7 correlated poorly with FEV1 before PEx (r = -.16, p = .02) and did not correlate with recovery to baseline FEV1 at end of treatment (r = .08, p = .22). Only 23/249 (9%) individual tests had a BD response in FEV1 of ≥12% and 200 ml. BD response was not related to age or severity of lung disease and led to an immediate change in clinical management in only four cases. CONCLUSIONS: Significant BD response in CF patients treated for PEx is rare, shows poor correlation with baseline pulmonary function and does not correlate with the recovery of FEV1 with treatment. These data suggest that routine testing for BD response is not indicated during PEx.

Asunto(s)

RESUMEN

INTRODUCTION: Investigations in associations between subjective health-related quality of life (HRQoL) measures and objective clinical assessments in patients with early-onset scoliosis (EOS) are limited. The purpose of this study is to investigate the association between pulmonary function rated by parents and pulmonary function testing (PFT) in patients with EOS. MATERIALS/METHODS: In this cross-sectional study, patients with EOS at any stage of treatment from 2011 to 2018 were identified in 2 registries including 33 centers. Parents' perception of pulmonary function was evaluated using pulmonary function (PF) domain in the Early-Onset Scoliosis 24 item Questionnaire (EOSQ-24). PFT measures included FVC% predicted, FEV1/FVC, and TLC% predicted. All PFT predicted values utilized arm span. PFT and EOSQ-24 questionnaire were completed within 180 days of each other with an average day difference of 26 days. RESULTS: 176 patients (mean age: 10.4 years old, female: 56%) were identified. 33% of patients were of congenital/structural etiology, 27% neuromuscular, 26% syndromic, and 14% idiopathic. Wide variance and lower scores of PF domain were reported by parents at lower FVC% predicted values (< 50%). As FVC% predicted values increased, PFD scores increased with simultaneous decreases in variance with few exceptions. CONCLUSION: More variability and frequent lower pulmonary function values are reported by parents when percent forced vital capacity (FVC%) is < 50%. This likely reflects the degree to which children adapt to restrictive lung disease and the limits on adaptation that occur increasingly as lung function falls below 50% predicted. As a direct linear association with high correlation was expected, more research into the character of what the PF domain is measuring is necessary. LEVEL OF EVIDENCE: IV.

Asunto(s)

RESUMEN

Peripheral (or small) airway obstruction (PAO) is considered a marker of childhood asthma but the techniques able to directly measure it are rarely used in routine. Usual spirometry and plethysmography can detect a certain degree of PAO when reduced forced vital capacity (FVC) is associated to normal forced expiratory volume in 1 s (FEV1 ) to FVC ratio, and normal total lung capacity (TLC). The frequency of this functional pattern has never been studied in different pediatric respiratory conditions. To assess the prevalence and outcome of PAO in children with different diseases or symptoms, we retrospectively extracted from our database all files of Caucasian subjects encompassing spirometry and plethysmography measurements. Spirometry patterns (normal, airflow limitation [AFL; low FEV1 /FVC], low FVC [with normal FEV1 /FVC]) and final functional patterns (normal, AFL, PAO, restrictive [low TLC], or mixed) were described. We included 4394 files recorded in 1794 children (median [IQR] age: 10.7 [9.2-12.9] years). At inclusion, 125 (7%) children had low FVC of which 56 (44.8%, and 3.1% [95% CI 2.3-3.9] of the whole population) had PAO. PAO prevalence increased with age (OR (95% CI) per 2-year-increase: 2.26 (1.59-3.23); p < .001), and was more frequent in chronic bronchial diseases other than asthma (1.6% vs. 8.0%). On repeated tests, PAO frequently normalized (26.1%) or persisted (43.5%), but it less often progressed into AFL (13%) or restrictive (13%) patterns. PAO is an infrequent nonspecific and persistent functional pattern. Its prevalence increases with age and in diagnosis of chronic respiratory diseases other than asthma.

Asunto(s)

RESUMEN

Progressive neuromuscular disease leads to muscle weakness or failure that produces loss of pulmonary function and clinical respiratory morbidity. Tracking pulmonary function in a practical and effective way is very important because it can help identify a stage of disease when a morbidity, such as inadequate airway clearance or respiratory failure, may be present. There are four general categories of pulmonary function outcome measures such as volume, flow, pressure, and gas exchange. These outcome measures have variable precision and accuracy in predicting clinical change, and practicality in performing them relative to age and condition. It is widely recommended to follow multiple measurements longitudinally and create an accurate and timely clinical picture. This manuscript will review the most commonly used and most practical measures for use in clinical practice and how they can help to assess morbidity, disease state, and help optimize patient management.

Asunto(s)

RESUMEN

Bronchiectasis (BE) is defined as a permanent, irreversible dilation of the bronchial tree. In the pediatric population, this disease process is most commonly associated with patients with cystic fibrosis (CF). However, BE unrelated to CF is increasingly noted as a cause of chronic respiratory related morbidity worldwide. Chronic inflammation and recurrent infection result in cellular cascades that lead to irreversible structural changes of the airways. When these architectural changes occur, they confer extensive risks to morbidity usually due to continued infections. In the adult population, BE has been associated with chronic obstructive pulmonary disease, which is mainly caused by cigarette smoking. In this report, the authors reviewed various cases of BE in the pediatric population at our institution. After a comprehensive case by case review, we compiled details of three cases of newly diagnosed BE where the most likely inciting factor was the electronic cigarette use. Common features of the three cases included at least a year of e-cigarette use with conjunction of tetrahydrocannabinol and radiologic findings of BE, ground glass opacities, and nodule formation.

Asunto(s)

Asunto(s)

RESUMEN

Pulmonary physiologic assessments are critical for the care and study of pediatric respiratory disease. In 2019, there were numerous contributions to this topic in Pediatric Pulmonology.

Asunto(s)

RESUMEN

BACKGROUND: Scoliosis is a common complication of severe neuromuscular diseases. The aim of this study is to determine the impact of posterior spinal fusion on pulmonary function parameters in patients with severe neuromuscular disease at our medical center. METHODS: Retrospective chart review of all patients with severe neuromuscular disease who had posterior spinal fusion between 2012 and 2017 at Texas Children's Hospital. Patients with growing rods, brain injury or malformation, and/or spina bifida were excluded. Pulmonary function measures before and after spinal surgery were determined. RESULTS: A total of 20 eligible patients were identified, 7 with Duchenne muscular dystrophy, 6 with spinal muscular atrophy, 3 with merosin deficient muscular dystrophy, 2 with Charcot-Marie-Tooth, 1 with central core disease, and 1 with dystroglycanopathy. The mean change in vital capacity from pre- to postspine surgery was a loss of 0.63 L for the spinal muscular atrophy patients, a loss of 0.36 L for the Duchenne muscular dystrophy patients, and a gain of 0.23 L for the merosin deficient patients. The difference between spinal muscular atrophy and merosin deficient patients was statistically significant (P = .02) CONCLUSION: In this single-center retrospective study, we found that after spine surgery for scoliosis, all patients with spinal muscular atrophy and most patients with Duchenne muscular dystrophy lost vital capacity, while the patients with merosin deficient muscular dystrophy gained vital capacity. These differences were not associated with differences is respiratory strength, body mass index, or surgical outcomes.

Asunto(s)

RESUMEN

BACKGROUND: The multiple breath washout (MBW) test may be most useful in tracking disease progression over time to inform treatment decisions. In the clinical setting, alternative outcomes, which can be obtained quickly and easily, may facilitate interpretation of clinically relevant changes in lung function. METHODS: In this secondary analysis of data from 78 cystic fibrosis (CF) and 72 healthy control (HC) subjects between the ages of 2.6 and 5.9 years, MBW was performed at enrollment, 1, 3, 6, 9, and 12 months, as well as during symptomatic visits using the Exhalyzer D (EcoMedics AG, Duernten, Switzerland). The lung clearance index, LCI2.5, was compared to moment ratios (M1 /M0 and M2 /M0 ) at the standard cutoff (1/40th of starting tracer gas concentration) as well as LCI5 and moment ratios at 1/20th of the starting concentration (M1 /M0 at LCI5 , and M2 /M0 at LCI5 ). RESULTS: All outcomes were able to distinguish between health and disease. LCI5 reduced testing time by 40% and increased feasibility by more than 10%. The limits of biological reproducibility in healthy children were similar between LCI2.5 (15%), LCI5 (12%), M1 /M0 at LCI2.5 (14%), and M1 /M0 at LCI5 (12%), but markedly larger for M2 /M0 at LCI2.5 (30%) and M2 /M0 at LCI5 (25%). Each outcome deteriorated significantly with worsening pulmonary symptoms, the magnitude of deterioration was greatest for M2 /M0 . CONCLUSIONS: In preschool children with CF, LCI5 was more feasible to obtain and track disease progression. The second moment ratio was most sensitive to pulmonary symptoms, but had the greatest variability both within and between subjects.

Asunto(s)

RESUMEN

RATIONALE: Obesity in children increases the risk for new asthma. How age, sex, race/ethnicity, and allergy status affect the relationship between obesity and asthma is unclear. This study describes the relationship between high body mass index (BMI) and incident asthma. METHODS: We conducted a retrospective cohort study to compare asthma incidence among normal weight, overweight, and obese 2 to 6, 7 to 11, and 12 to 17 year olds to define the effects of sex, race/ethnicity, and allergy status. Weight status was determined at baseline and asthma incidence was defined as ≥2 asthma encounters and ≥1 asthma prescriptions. We used multivariable Poisson regression to estimate adjusted incident asthma rates and risk ratios. RESULTS: Data from 192 843 2 to 6 year olds, 157 284 7 to 11 year olds, and 157 369 12 to 17 year olds were included. The relative risks (95% confidence interval [CI]) of new asthma among obese children in 2 to 6 year olds, 7 to 11 year olds, and 12 to 17 year olds were 1.25 (1.15, 1.37), 1.49 (1.32, 1.69) and 1.40 (1.21, 1.63), respectively. Among children with underlying allergic rhinitis, obesity did not increase the risk of new asthma. In children without allergic rhinitis, the risk for obesity-related asthma was highest in 7 to 11 year olds (risk ratio = 1.50 95% CI, 1.33, 1.60). Before age 12, females had a higher risk for obesity-related asthma; but after age 12, obese males had a higher asthma risk (interaction P-value < .05). CONCLUSION: Obesity is a major preventable risk factor for pediatric asthma that appears to vary along the pediatric age continuum and depends on sex, race/ethnicity and atopy status.

Asunto(s)