Persistent and symptomatic periodic breathing beyond the neonatal period in full-term infants: A case series.

INTRODUCTION: Periodic breathing (PB) is considered physiological in the neonatal period and usually disappears in the first months of life. There are few data available on persistent PB after the neonatal period. The objective of this study was to characterize infants born at term with persistent PB after the age of 1 month through polysomnography (PSG) performed during symptoms. METHODS: This retrospective case series included infants born at term between 2012 and 2021, without an underlying disease, who presented with symptoms of persistent PB during a PSG. Persistent PB was defined as more than 1 % of total sleep time (TST) of PB after 1 month of life, and PB was defined as a succession of at least three episodes of central apnea lasting more than 3 s and separated by less than 20 s of normal breathing. RESULTS: A total of 10 infants born at term were included. They underwent PSG for brief resolved unexplained events, desaturation, pauses in breathing, cyanosis, and/or signs of respiratory distress. The percentage of TST spent with PB was 18.1 % before 3 months of age (n = 7), and 4.7 % between 3 and 6 months of age (n = 10). During the first PSG, ≥3 % of desaturation events were observed in 77-100 % of the PB episodes. At the first PSG, nine of the 10 infants had an obstructive apnea-hypopnea index of >10/h and five of 10 infants had a central apnea index of >5/h. Gastroesophageal reflux (GER) was suspected in eight infants. All infants showed improvement in the initial symptoms during the first year of life. CONCLUSION: This study presents cases of persistent and symptomatic PB after 1 month of life in infants born at term. The interesting finding was the presence of obstructive sleep apnea syndrome and/or central apnea syndrome in the majority of children, along with GER.

Short-term cognitive loading deteriorates breathing pattern and gas exchange in adult patients with congenital central hypoventilation syndrome.

Question: Human PHOX2B mutations result in life-threatening sleep-related hypoventilation (congenital central hypoventilation syndrome, CCHS). Most patients retain ventilatory activity when awake through a respiratory-related cortical network. We hypothesised that this need to mobilise cortical resources to breathe would lead to breathing-cognition interferences during cognitive loading. Patients and methods: Seven adult CCHS patients (five women; median age 21) performed standard neuropsychological tests (paced auditory serial addition test - calculation capacity, working memory, sustained and divided attention; trail making test - visuospatial exploration capacity, cognitive processing speed, attentional flexibility; Corsi block-tapping test - visuospatial memory, short-term memory, working memory) during unassisted breathing and under ventilatory support. Ventilatory variables and transcutaneous haemoglobin oxygen saturation were recorded. Cortical connectivity changes between unassisted breathing and ventilatory support were assessed using electroencephalographic recordings (EEG). Results: Baseline performances were lower than expected in individuals of this age. During unassisted breathing, cognitive loading coincided with increased breathing variability, and decreases in oxygen saturation inversely correlated with an increasing number of apnoeic cycles per minute (rho -0.46, 95% CI -0.76 to -0.06, p=0.01). During ventilatory support, cognitive tasks did not disrupt breathing pattern and were not associated with decreased oxygen saturation. Ventilatory support was associated with changes in EEG cortical connectivity but not with improved test performances. Conclusions: Acute cognitive loads induce oxygen desaturation in adult CCHS patients during unassisted breathing, but not under ventilatory support. This justifies considering the use of ventilatory support during mental tasks in CCHS patients to avoid repeated episodes of hypoxia.

Respiratory function and sleep in children with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease in children causing sleep and respiratory disorders that are poorly described in the literature compared to adult forms. This retrospective observational study was performed at the Armand Trousseau University Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. We retrospectively collected data from lung function tests, nocturnal gas exchange recordings, and polysomnography of 24 children with DM1. 39% of the children with DM1 reported respiratory symptoms indicative of sleep disordered breathing. Three patients (12%) presented with a restrictive respiratory pattern, 10 (42%) with a sleep apnoea syndrome, mainly of obstructive origin (2/10 with severe obstructive sleep apnea syndrome), and 11 (45%) with nocturnal alveolar hypoventilation. Non-invasive ventilation (NIV) was indicated in 9 (37.5%) children, although tolerance was poor. No significant deterioration in respiratory function or nocturnal gas exchange was observed during the NIV-free period. This study provides new and useful insights into DM1 disease evolution in children to better adapt for respiratory follow-up and management. This highlights the need for future research to better understand the origin of respiratory and sleep disorders in patients with DM1.

Children's views on artificial intelligence and digital twins for the daily management of their asthma: a mixed-method study.

New technologies enable the creation of digital twin systems (DTS) combining continuous data collection from children's home and artificial intelligence (AI)-based recommendations to adapt their care in real time. The objective was to assess whether children and adolescents with asthma would be ready to use such DTS. A mixed-method study was conducted with 104 asthma patients aged 8 to 17 years. The potential advantages and disadvantages associated with AI and the use of DTS were collected in semi-structured interviews. Children were then asked whether they would agree to use a DTS for the daily management of their asthma. The strength of their decision was assessed as well as the factors determining their choice. The main advantages of DTS identified by children were the possibility to be (i) supported in managing their asthma (ii) from home and (iii) in real time. Technical issues and the risk of loss of humanity were the main drawbacks reported. Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. Those with the best computer skills were more likely to choose the DTS, while those who placed a high value on the physician-patient relationship were less likely to do so.   Conclusions: The majority of children were ready to use a DTS for the management of their asthma, particularly if it was more effective than current care. The results of this study support the development of DTS for childhood asthma and the evaluation of their effectiveness in clinical trials. What is Known: • New technologies enable the creation of digital twin systems (DTS) for children with asthma. • Acceptance of these DTSs by children with asthma is unknown. What is New: • Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. •Children identified the ability to be supported from home and in real time as the main benefits of DTS.

COVID-19 and pediatric pulmonology: Feedback from an expert center after the first year of the pandemic.

The coronavirus disease 2019 (COVID-19) outbreak has evolved with different waves corresponding to subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. While the most severe cases have been observed in the elderly and in individuals with underlying comorbidities, severe pediatric and young adult cases have been observed, as well as post-infectious inflammatory syndromes and persistent symptoms leading to long-COVID. This manuscript describes the experience of a pediatric respiratory unit during the first year of the pandemic and reviews the corresponding literature with a special emphasis on children and young people with underlying conditions, such as immunosuppression, sickle cell disease, and cystic fibrosis.

SARS-CoV-2 B.1.1.529 (Omicron) Variant Causes an Unprecedented Surge in Children Hospitalizations and Distinct Clinical Presentation Compared to the SARS-CoV-2 B.1.617.2 (Delta) Variant.

Background: In the midst of successive waves of SARS-CoV-2 variants, the B.1.1.529 (omicron) variant has recently caused a surge in pediatric infections and hospitalizations. This study aimed to describe and compare the symptoms, explorations, treatment and evolution of COVID-19 in hospitalized children during the successive B.1.617.2 (delta) and B.1.1.529 (omicron) waves. Methods: This observational study was performed in the Pediatric Pulmonology Department of a University Hospital in Paris, France. All hospitalized children aged between 0 and 18 years who tested positive for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs from July 15th to December 15th 2021 (delta wave), and from December 15th 2021 to February 28th 2022 (omicron wave) were included. Results: In total, 53 children were included, 14 (26.4%) during the delta wave and 39 (73.6%) during the omicron wave (almost three times as many hospitalizations in half the time during the latter wave). During the omicron wave, hospitalized patients were mostly aged < 5 years (90 vs. 71% of all the children during omicron and delta waves, respectively), and tended to have fewer underlying conditions (56 vs. 79% during omicron and delta waves, respectively, p = 0.20). The omicron variant was also responsible for a different clinical presentation when compared to the delta variant, with significantly higher and often poorly tolerated temperatures (p = 0.03) and increased digestive symptoms (p = 0.01). None of the three patients who were older than 12 years were fully vaccinated. Conclusion: The dramatic increase in the hospitalization of children with COVID-19 and the modification of the clinical presentation between the latest delta and omicron waves require pediatricians to remain vigilant. It should also encourage caregivers to ensure vaccination in children older than 5 years, for whom the BNT162b2 COVID-19 vaccine has been deemed safe, immunogenic, and effective.

High Nasal Nitric Oxide, Cilia Analyses, and Genotypes in a Retrospective Cohort of Children with Primary Ciliary Dyskinesia.

Rationale: Although children with primary ciliary dyskinesia (PCD) typically have low nasal nitric oxide (nNO), some children with indisputable PCD may have unexplained high nNO concentrations. Objectives: To look for relationships between nNO measures and genetic findings (and cilia motility or ultrastructure when available) in children with PCD with known genotypes. Methods: We retrospectively studied 73 children with PCD (median age, 9.5 [range, 2.1-18.2] yr). nNO was the mean value of a plateau reached while the velum was closed (nNO-VC; threshold, 77 nl ⋅ min-1) or was calculated as the average of five peaks obtained during tidal breathing (threshold, 40 nl ⋅ min-1). Ciliary beat was classified as either motile (including dyskinetic pattern) or immotile, depending on whether motility was present or absent in all cilia, or as a mixture of motile and immotile cilia. Genotypes were classified as pathogenic mutations in genes known to be associated with high nNO (mild genotype), biallelic truncating mutations in other genes (severe mutations), or putative hypomorphic pathogenic mutations (missense, single amino acid deletion, or moderate splicing mutations) in at least one allele believed to be possibly associated with residual production of a functional protein. Results: nNO was above the discriminant threshold in 16 of 73 (21.9%) children (11 nNO-VC and 5 nNO during tidal breathing). High nNO was less frequent in children with severe mutations (2 of 42) than in those with mild genotypes (7 of 10) or at least one hypomorphic mutation (7 of 21) (P < 0.0001). Median (interquartile range) nNO-VC values (n = 60) were significantly different in the three genotype groups: severe mutations, 18 (10-26) nl ⋅ min-1 (n = 36); possible residual functional protein production (putative hypomorphic mutations), 23 (16-68) nl ⋅ min-1 (n = 17); and mild genotypes, 139 (57-216) nl ⋅ min-1 (n = 7) (P = 0.0002). The higher the cilia motility, the higher the nNO-VC (16 [10-23], 23 [17-56], and 78 [45-93] nl ⋅ min-1 in patients with immotile, dyskinetic motile and immotile, and dyskinetic motile cilia, respectively; P < 0.0001), while nNO values were scattered across different ultrastructure defects (P = 0.07). Conclusions: In children with PCD, high nNO values were linked not only to specific genes but also to potentially hypomorphic mutations in other genes (with possible functional protein production). nNO values increased with the proportion of motile cilia.

Respiratory management of spinal muscular atrophy type 1 patients treated with Nusinersen.

INTRODUCTION: The recent development of disease-modifying treatments in spinal muscular atrophy (SMA) type 1 shifted these patients' management from palliative to proactive. The aim of this study was to assess patients' nocturnal gas exchanges before noninvasive ventilation (NIV) initiation and their clinical evolution to determine if capnia is a good criterion to decide when to introduce respiratory support. PATIENTS AND METHODS: This multicentric retrospective study reports the respiratory management and evolution of 17 SMA type 1 children (10 females) for whom treatment with Nusinersen was initiated between 2016 and 2018. RESULTS: Median [interquartile range-IQR] age at diagnosis and at first Nusinersen injection was of 4 [3;8] and 4 [3;9] months, respectively. Patients were followed during 38 [24;44] months. Thirteen (76%) patients were started on NIV at a median [IQR] age of 12 [9;18] months. Repeated hospitalizations and intensive care unit admissions were needed for 11 of them. Blood gas and nocturnal gas exchange recordings performed before NIV initiation were always normal. 9/13 X-ray performed before NIV showed atelectasis and/or acute lower respiratory tract infections. There was a significant decrease in the total number of hospital admissions between the first and second year of treatment (p = 0.04). CONCLUSION: This study shows that patients do not present with nocturnal hypoventilation before respiratory decompensations and NIV initiation, and suggests that a delay in NIV initiation might result in respiratory complications. There is a need for disease-centered guidelines for the respiratory management of these patients, including NIV indications.

Evaluation of obesity and asthma as risk factors for moderate to severe obstructive sleep apnea in children.

STUDY OBJECTIVES: Asthma and obesity are risk factors for obstructive sleep apnea (OSA) in children but their link to OSA severity is uncertain. We aimed at determining whether asthma or obesity was associated with an increased risk of moderate/severe OSA. METHODS: Children undergoing a one-night polysomnography for suspicion of OSA were retrospectively included. Univariate and multivariate analyses were conducted to assess the clinical and demographic characteristics linked to moderate/severe OSA (obstructive apnea-hypopnea index ≥ 5 events/h of sleep) with odds ratio and 95% confidence interval reported. RESULTS: Four hundred ninety children (311 [64%] boys) were included with a median [25th; 75th percentile] age of 8.7 [5.4; 12.9] years, 164 (33%) nonasthmatics nonobese, 122 (25%) obese nonasthmatics, 125 (26%) asthmatics nonobese, 79 (16%) asthmatics and obese. Moderate/severe OSA was present in 157 (32%) children (75/157 [48%] obese and 52/157 [33%] asthmatics). Independent factors associated with increased or decreased risk of moderate/severe OSA were obesity and male sex (odds ratio 1.82 [1.16; 2.87], P = .01, and 1.55 [1.02; 2.36], P = .04, respectively), and current asthma, age > 6 years, or behavioral disorders (odds ratio 0.45 [0.29; 0.70], P < .001; 0.44 [0.27; 0.73], P < .001; and 0.55 [0.33; 0.92], P = .02, respectively). Abnormal resistance of the respiratory system (measured in 241 children), but not abnormal spirometry (measured in 213 children), increased the risk of moderate/severe OSA (odds ratio 2.95 [1.46-5.96], P = .003). CONCLUSIONS: In our cohort enriched in obese and asthmatic children, obesity was associated with higher risk of moderate/severe OSA whereas current asthma was not. CITATION: Ioan I, Mulier G, Taytard J, Césaire A, Beydon N. Evaluation of obesity and asthma as risk factors for moderate to severe obstructive sleep apnea in children. J Clin Sleep Med. 2022;18(6):1639-1648.

Impact of inspiratory threshold loading on brain activity and cognitive performances in healthy humans.

In healthy humans, inspiratory threshold loading deteriorates cognitive performances. This can result from motor-cognitive interference (activation of motor respiratory-related cortical networks vs. executive resources allocation), sensory-cognitive interference (dyspnea vs. shift in attentional focus), or both. We hypothesized that inspiratory loading would concomitantly induce dyspnea, activate motor respiratory-related cortical networks, and deteriorate cognitive performance. We reasoned that a concomitant activation of cortical networks and cognitive deterioration would be compatible with motor-cognitive interference, particularly in case of a predominant alteration of executive cognitive performances. Symmetrically, we reasoned that a predominant alteration of attention-depending performances would suggest sensory-cognitive interference. Twenty-five volunteers (12 men; 19.5-51.5 yr) performed the Paced Auditory Serial Addition Test (PASAT-A and B; calculation capacity, working memory, attention), the Trail Making Test (TMT-A, visuospatial exploration capacity; TMT-B, visuospatial exploration capacity, and attention), and the Corsi block-tapping test (visuospatial memory, short-term, and working memory) during unloaded breathing and inspiratory threshold loading in random order. Loading consistently induced dyspnea and respiratory-related brain activation. It was associated with deteriorations in PASAT-A [52 [45.5;55.5]; (median [interquartile range]) to 48 [41;54.5], P = 0.01], PASAT-B (55 [47.5;58] to 51 [44.5;57.5], P = 0.01), and TMT-B (44 s [36;54.5] to 53 s [42;64], P = 0.01), but did not affect TMT-A and Corsi. The concomitance of cortical activation and cognitive performance deterioration is compatible with competition for cortical resources (motor-cognitive interference), whereas the profile of cognitive impairment (PASAT and TMT-B but not TMT-A and Corsi) is compatible with a contribution of attentional distraction (sensory-cognitive interference). Both mechanisms are therefore likely at play.NEW & NOTEWORTHY To our knowledge, this is the first study exploring the interferences between inspiratory loading and cognition in healthy subjects with the concomitant use of neuropsychological tests and electroencephalographic recordings. Inspiratory loading was associated with dyspnea, respiratory-related changes in brain activation, and a pattern of deterioration of neuropsychological tests suggestive of attentional disruption. Inspiratory loading is therefore likely to impact cognitive performances through both motor-cognitive interference (engagement of cortical networks) and sensory-cognitive interference (dyspnea-related shift in attentional focus).

Estimating pulmonary function after surgery for adolescent idiopathic scoliosis using biplanar radiographs of the chest with 3D reconstruction.

AIMS: This study addressed two questions: first, does surgical correction of an idiopathic scoliosis increase the volume of the rib cage, and second, is it possible to evaluate the change in lung function after corrective surgery for adolescent idiopathic scoliosis (AIS) using biplanar radiographs of the ribcage with 3D reconstruction? METHODS: A total of 45 patients with a thoracic AIS which needed surgical correction and fusion were included in a prospective study. All patients underwent pulmonary function testing (PFT) and low-dose biplanar radiographs both preoperatively and one year after surgery. The following measurements were recorded: forced vital capacity (FVC), slow vital capacity (SVC), and total lung capacity (TLC). Rib cage volume (RCV), maximum rib hump, main thoracic curve Cobb angle (MCCA), medial-lateral and anteroposterior diameter, and T4-T12 kyphosis were calculated from 3D reconstructions of the biplanar radiographs. RESULTS: All spinal and thoracic measurements improved significantly after surgery (p < 0.001). RCV increased from 4.9 l (SD 1) preoperatively to 5.3 l (SD 0.9) (p < 0.001) while TLC increased from 4.1 l (SD 0.9) preoperatively to 4.3 l (SD 0.8) (p < 0.001). RCV was correlated with all functional indexes before and after correction of the deformity. Improvement in RCV was weakly correlated with correction of the mean thoracic Cobb angle (p = 0.006). The difference in TLC was significantly correlated with changes in RCV (p = 0.041). It was possible to predict postoperative TLC from the postoperative RCV. CONCLUSION: 3D rib cage assessment from biplanar radiographs could be a minimally invasive method of estimating pulmonary function before and after spinal fusion in patients with an AIS. The 3D RCV reflects virtual chest capacity and hence pulmonary function in this group of patients. Cite this article: Bone Joint J 2022;104-B(1):112-119.

Benefits and risks of bronchoalveolar lavage in severe asthma in children.

BACKGROUND: Although bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management. MATERIAL AND METHODS: The study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included. RESULTS: In total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p<0.001). BAL induced a therapeutic modification only for azithromycin and omalizumab prescriptions. The practice of a BAL decreased bronchoscopy tolerance (p=0.037), especially in the presence of tracheobronchial malacia (p<0.01) and when performed in a symptomatic patient (p=0.019). DISCUSSION AND CONCLUSION: Although BAL may provide interesting information in characterising severe asthma, in most cases its impact on the patient's management remains limited. Moreover, BAL can be poorly tolerated and should be avoided in the case of tracheobronchial malacia or current asthma symptoms.

Improvement in Asthma Symptoms and Pulmonary Function in Children After SARS-CoV-2 Outbreak.

Introduction: Little is known on the effect of SARS-CoV-2 circulation on asthma daily symptoms in children. We compared asthma exacerbations, asthma symptom control and lung function before and after SARS-CoV-2 outbreak in children. Methods: Retrospective study of children with persistent asthma referred for lung function testing. The second quarter of 2020 being a period with nearly no activity, we compared the activity between the first, third and fourth quarters of 2019 and 2020 (Q1-2019 vs. Q1-2020, Q3-2019 vs. Q3-2020 and Q4-2019 vs. Q4-2020). Results: We retrieved 1,871 files in 2019 and 1,548 in 2020. The whole population [2,165 (63.3%) boys] had a median [IQR] age of 9.7 [6.8;13.1] years. There was no difference in age, sex, and ethnicity between 2019 and 2020 populations. Asthma was better controlled during Q4-2020 compared to Q4-2019 (P = 0.042), and there was a lower proportion of children with at least one exacerbation in the previous 3 months after the reopening, compared to the same period in 2019 (P < 0.0001). Baseline FEV1 (Z-score) recorded after the reopening was significantly higher (with less reversibility) compared to the same period before the epidemic (P < 0.0001). Baseline FEV1/FVC (Z-score) was significantly higher during Q3-2020 compared to Q3-2019 (P = 0.026), with fewer children having a significant reversibility (P = 0.035). Discussion: We demonstrated a trend toward increased exacerbations just before the recognition of the epidemic, and fewer exacerbations, better asthma symptom control and improvement in the lung function of asthmatic children after the reopening.

Paediatric long term continuous positive airway pressure and noninvasive ventilation in France: A cross-sectional study.

OBJECTIVE: To describe the characteristics of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in France. DESIGN: Cross-sectional national survey. SETTING: Paediatric CPAP/NIV teams of 28 tertiary university hospitals in France. PATIENTS: Children aged <20 years treated with CPAP/NIV since at least 3 months on June 1st, 2019. INTERVENTION: An anonymous questionnaire was filled in for every patient. RESULTS: The data of 1447 patients (60% boys), mean age 9.8 ± 5.8 years were analysed. The most frequent underlying disorders were: upper airway obstruction (46%), neuromuscular disease (28%), disorder of the central nervous system (13%), cardiorespiratory disorder (7%), and congenital bone disease (4%). Forty-five percent of the patients were treated with CPAP and 55% with NIV. Treatment was initiated electively for 92% of children, while 8% started during an acute illness. A poly(somno)graphy (P(S)G) was performed prior to treatment initiation in 26%, 36% had a P(S)G with transcutaneous carbon dioxide monitoring (PtcCO2), while 23% had only a pulse oximetry (SpO2) with PtcCO2 recording. The decision of CPAP/NIV initiation during an elective setting was based on the apnea-hypopnea index (AHI) in 41% of patients, SpO2 and PtcCO2 in 25% of patients, and AHI with PtcCO2 in 25% of patients. Objective adherence was excellent with a mean use of 7.6 ± 3.2 h/night. Duration of CPAP/NIV was 2.7 ± 2.9 years at the time of the survey. CONCLUSION: This survey shows the large number of children treated with long term CPAP/NIV in France with numerous children having disorders other than neuromuscular diseases.

Peripheral obstruction without airflow limitation is rare and not specific to asthma in children.

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.