SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

The Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age.

BACKGROUND: Recent attempts to refine the definition bronchopulmonary dysplasia (BPD) have based its predictive capacity on respiratory outcome in the first 2 years of life, eliminating the pre-existing requirement of 28 days of oxygen therapy prior to 36 weeks postmenstrual age (PMA). The objective of this study was to assess the utility of the 2001 consensus definition in predicting impaired lung function at preschool age. METHODS: This cohort study included children aged 4-6 years old who were born at gestational age (GA) <32 weeks or bodyweight <1500 g. Univariate and multivariate analyses were performed to assess differences in antenatal and neonatal variables between BPD and non-BPD children. All participants underwent incentive spirometry. Lung function parameters were contrasted with the Global Lung Function Initiative (GLI-2012) reference equations and, together with antenatal and neonatal variables, compared among the different subgroups (no BPD, mild BPD, and moderate-to-severe BPD). A multivariate model was generated to identify independent risk factors for impaired lung function. RESULTS: GA, hemodynamically significant patent ductus arteriosus, and late sepsis were independent risk factors for the development of BPD. A total of 119 children underwent incentive spirometry. All lung function parameters were significantly altered relative to reference values. Greater impairment of lung function was observed in the mild BPD vs. the no BPD group (forced expiratory volume in the first 0.75 seconds [FEV0.75]: -1.18 ± 0.80 vs. -0.55 ± 1.13; p = 0.010), but no difference in forced vital capacity (FVC) was observed (-0.32 ± 0.90 vs. -0.18 ± 1; p = 0.534). The moderate-to-severe BPD group exhibited the most severe FEV0.75 reduction (FEV0.75: -2.63 ± 1.18 vs. -0.72 ± 1.08; p = 0.000) and was the only condition with FVC impairment (FVC: -1.82 ± 1.12 vs. -0.22 ± 0.87; p = 0.000). The multivariate analysis identified a diagnosis of moderate-to-severe BPD as an independent risk factor for lung function impairment. CONCLUSION: The 2001 consensus definition of BPD has adequate predictive capacity for lung function measured by spirometry at 4-6 years of age. Moderate-to-severe BPD was the best predictor of respiratory impairment. Children with mild BPD showed greater alteration of FEV0.75 than those without BPD.

The Nurse's Role in Educating Pediatric Patients on Correct Inhaler Technique: An Interventional Study.

The prevalence of pediatric respiratory diseases in Spain is 23%. Inhalation is the preferred route of administration but there are frequent errors in the performance of the inhalation technique leading a poor control of the disease. The aim of this research was to detect errors in the execution of the inhalation technique at a Pediatric Pulmonology Unit in a hospital of Aragón (Spain). In order to improve the administration of inhaled medication, an educational intervention for 1 year by nursing was conducted. This interventional study, including children aged 1 to 15 years with an inhalation therapy and who attended the Pediatric Pulmonology Unit, was conducted between September 2017 and September 2018. Logistic Regression models were conducted in SPSS. This study involved 393 children (61.1% boys). Before the intervention, 39.4% achieved a correct inhalation technique increasing up to 62.1% after the intervention. Those who had their first visit to the Unit, young children and girls had a higher risk of incorrect performance than those with subsequent visits, older children, and boys, respectively. The most common errors in the inhalation technique were not performing adequate apnoea after inhaling and not rinsing the mouth at the end of the procedure. The education given by nurses to pediatric patients improved the inhalation technique, achieving better control of the disease and use of the health system.

Incidence and Prevalence of Children's Diffuse Lung Disease in Spain.

BACKGROUND: Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain. METHODS: Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019. RESULTS: A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28-10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81-51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2-18 years of age compared with children 0-2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47). CONCLUSIONS: We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases.

[Adverse drug reactions of montelukast: from theory to practice. Case report]. / Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos.

Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos Adverse drug reactions of montelukast: from theory to practice. Case report were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.

El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.

Neonatal cystic fibrosis screening: Analysis and differences in immunoreactive trypsin levels in newborns with a positive screen.

INTRODUCTION: Neonatal cystic fibrosis (CF) screening has enabled the disease to be diagnosed early, and is a determining factor in the increase in survival of these patients. Its main disadvantage is its low specificity and elevated number of false positives. The aim of this study is to analyse the differences in immunoreactive trypsin (IRT) between the different groups of newborns (NB) with a positive neonatal screen depending on whether they were healthy, healthy carriers, affected by CF, or CFSPID (Cystic Fibrosis Screen Positive, Inconclusive Diagnosis). MATERIAL: Retrospective analytical study of the concentrations of IRT in NB with a positive neonatal screen for CF born in a tertiary hospital during an 8-year period. RESULTS: A total of 790 NB with a positive neonatal screen for CF were analysed. Of these 86.3% were term, 53% girls, and 11.8% were admitted. The mean IRT value was 79.16 ng/mL (range 60-367). Significantly higher concentrations of IRT were found in those affected by CF compared to the other groups (P < .001). There were higher levels in large prematures (P = .007) and admitted patients (P = .002). There were no differences as regards gender or season. There was a direct correlation of 64% (P = .001) between IRT and sweat test in those affected by CF and CFSPID. A cut-off value of IRT for the diagnosis of CF was calculated from the ROC curve (76.2 ng/mL (S = 95.7%, Sp = 64.5%). CONCLUSIONS: NB with CF have significantly higher levels of IRT than healthy ones, or carriers and CFSPID. Prematurity and hospital admission may also have an influence. A higher IRT value is associated with a higher level in the sweat test.

Implementation of a Gene Panel for Genetic Diagnosis of Primary Ciliary Dyskinesia. / Implementación de un panel de genes para el diagnóstico genético de la discinesia ciliar primaria.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients. METHODS: This was a multicenter cross-sectional study of patients with a high suspicion of PCD, according to European Respiratory Society criteria, designed around a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD. RESULTS: We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature. CONCLUSIONS: The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches.

[Common variable immunodeficiency. Prognostic factors for lung damage]. / Inmunodeficiencia común variable: factores pronósticos de lesión pulmonar.

BACKGROUND AND OBJECTIVE: Lung damage is considered to be key to Common Variable Immunodeficiency (CVID) prognosis. We describe lung damage in pediatric CVID patients and assess its relationship with memory B cells (MB) phenotype, immunoglobulin G (IgG) levels at the time of diagnosis, and diagnostic delay. We also assessed the prevalence of allergy and autoimmune phenomena. PATIENTS AND METHOD: Cross-sectional study of 17 CVID patients treated at Vall d'Hebron University Hospital. Prevalence ratio and prevalence odds ratio were used to assess the effect of MB cells phenotype, IgG levels and diagnostic delay on lung damage. RESULTS: Five of seventeen patients presented bronchiectasis. Diagnostic delay >5 years was significantly associated with more severe lung damage. MBO phenotype and low IgG levels at the time of diagnosis showed a trend to more severe lung damage without reaching statistical signification. A higher prevalence of allergic or autoimmune phenomena was not observed. CONCLUSIONS: Latter diagnosis is associated with greater lung damage in CVID patients. The study of MB cells should be included in the study of these patients.

[Chest deformity as a cause of tracheobronchial compression. A pediatric case]. / Deformidad torácica como causa de compresión traqueobronquial. A propósito de un caso clínico pediátrico.

Idiopathic scoliosis is the abnormal flexion and rotation of the vertebral bodies, causing respiratory symptoms and altered pulmonary function. Straight back syndrome is a decreased in the anteroposterior diameter of the thorax. We present a 13-year-old patient with idiopathic scoliosis who Deformidad torácica como causa de compresión traqueobronquial. A propósito de un caso clínico pediátrico Chest deformity as a cause of tracheobronchial compression. A pediatric case developed progressive dyspnea, inspiratory stridor and a significant decrease in pulmonary function, because of extrinsic compression of the right main bronchus and the middle third of trachea by the thoracic vertebral bodies. She had also a decreased anteroposterior diameter of the thorax, being a determining factor in the appearance of symptoms. Surgery was performed by thoracic vertebra fixation T3 to T11, with subsequent clinical and functional respiratory improvement. Scoliosis associated with altered pulmonary function and stridor should make us suspect the existence of airway compression, especially in patients with reduction of the anteroposterior diameter of the thorax.

La escoliosis idiopática es la flexión y rotación anómala de los cuerpos vertebrales, que puede causar sintomatología respiratoria y alteración de función pulmonar. El síndrome de la espalda recta es una alteración caracterizada por una disminución del diámetro anteroposterior del tórax. Se presenta a una paciente de 13 años afectada de escoliosis idiopática que desarrolló disnea de esfuerzo progresiva, estridor inspiratorio y disminución importante de función pulmonar, secundaria a compresión extrínseca del bronquio principal derecho y tercio medio traqueal por cuerpos vertebrales torácicos. A su vez, tenía una disminución del diámetro anteroposterior del tórax, factor determinante en la aparición de los síntomas. Se intervino mediante fijación de vértebra torácica T3-T11, con posterior mejoría clínica y funcional respiratoria. La escoliosis asociada a alteración de función pulmonar y estridor debe hacer sospechar la existencia de compresión de la vía aérea, especialmente, en pacientes con reducción del diámetro anteroposterior del tórax.

Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspicion of PCD. Sixty-eight (91.9%) patients were evaluable for all tested antibodies. Thirty-three cases (44.6%) presented an absence or mislocation of protein in the ciliary axoneme (15 absent and 3 proximal distribution of DNAH5 in the ciliary axoneme, 3 absent DNAH5 and DNALI1, 7 absent DNALI1 and cytoplasmatic localization of GAS8, 1 absent GAS8, 3 absent RSPH9 and 1 absent RSPH4A). Fifteen patients had confirmed or highly likely PCD but normal immunofluorescence results (68.8% sensitivity and 100% specificity). In conclusion, immunofluorescence analysis is a quick, available, low-cost and reliable diagnostic test for PCD, although it cannot be used as a standalone test.

Validation of Global Lung Function Initiative and All Ages Reference Equations for Forced Spirometry in Healthy Spanish Preschoolers. / Validación de las ecuaciones propuestas por la Iniciativa Global de Función Pulmonar (GLI) y las de Todas las Edades para espirometría forzada en preescolares sanos españoles.

INTRODUCTION: Recent publication of multi-ethnic spirometry reference equations for subjects aged from 3-95 years aim to avoid age-related discontinuities and provide a worldwide standard for interpreting spirometric test results. OBJECTIVES: To assess the agreement of the Global Lung Function Initiative (GLI-2012) and All ages (FEV0.5) reference equations with the Spanish preschool lung function data. To verify the appropriateness of these reference values for clinical use in Spanish preschool children. METHODS: Spirometric measurements were obtained from children aged 3 to 6 years attending 10 randomly selected schools in Barcelona (Spain). Stanojevic's quality control criteria were applied. Z-scores were calculated for the spirometry outcomes based on the GLI equations. If the z-score (mean) of each parameter was close to 0, with a maximum variance of ± 0.5 from the mean and a standard deviation of 1, the GLI-2012 equations would be applicable in our population. RESULTS: Of 543 children recruited, 405 (74.6%) were 'healthy', and of these, 380 were Caucasians. Of these 380, 81.6% (169 females, 141 males) performed technically acceptable and reproducible maneuvers to assess FEVt, and 69.5% achieved a clear end-expiratory plateau. Z-scores for FVC, FEV1, FEV1/FVC, FEV0.75, FEV0.75/FVC, FEV0.5, FEF75 and FEF25-75 all fell within ± 0.5, except for FEV1/FVC (0.53 z-scores). CONCLUSIONS: GLI equations are appropriate for Spanish preschool children. These data provide further evidence to support widespread application of the GLI reference equations.

[Evaluation of dysphagia. Results after one year of incorporating videofluoroscopy into its study]. / Evaluación de la disfagia. Resultados tras un año de la incorporación de la videofluoroscopia en nuestro centro.

INTRODUCTION: Dysphagia is very common in children with neurological disabilities. These patients usually suffer from respiratory and nutritional problems. The videofluoroscopic swallowing study (VFSS) is the most recommended test to evaluate dysphagia, as it shows the real situation during swallowing. OBJECTIVES: To analyse the results obtained in our centre after one year of the implementation of VFSS, the clinical improvement after confirmation, and the prescription of an individualised treatment for the patients affected. MATERIAL AND METHODS: VFSS performed in the previous were collected. The following variables were analysed: age, pathology, degree of neurological damage, oral and pharyngeal and/or oesophageal dysphagia and its severity, aspirations, prescribed treatment, and nutritional and respiratory improvement after diagnosis. A statistical analysis was performed using SPSS v21. RESULTS: A total of 61 VFSS were performed. Dysphagia was detected in more than 70%, being moderate-severe in 58%. Aspirations and/or penetrations were recorded in 59%, of which 50% were silent. Adapted diet was prescribed to 56%, and gastrostomy was performed on 13 (21%) patients. A statistical association was found between neurological disease and severity of dysphagia. The degree of motor impairment is related to the presence of aspirations. After VFSS evaluation and treatment adjustment, nutritional improvement was found in Z-score of weight (+0.3SD) and BMI (+0.4SD). There was respiratory improvement in 71% of patients with dysphagia being controlled in the Chest Diseases Department. CONCLUSIONS: After implementation of VFSS, a high percentage of patients were diagnosed and benefited from a correct diagnosis and treatment. VFSS is a fundamental diagnostic test that should be included in paediatric centres as a diagnostic method for children with suspected dysphagia.

Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos / Adverse drug reactions of montelukast: from theory to practice. Case report

El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.

Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.

Deformidad torácica como causa de compresión traqueobronquial. A propósito de un caso clínico pediátrico / Chest deformity as a cause of tracheobronchial compression. A pediatric case

La escoliosis idiopática es la flexión y rotación anómala de los cuerpos vertebrales, que puede causar sintomatología respiratoria y alteración de función pulmonar. El síndrome de la espalda recta es una alteración caracterizada por una disminución del diámetro anteroposterior del tórax. Se presenta a una paciente de 13 años afectada de escoliosis idiopática que desarrolló disnea de esfuerzo progresiva, estridor inspiratorio y disminución importante de función pulmonar, secundaria a compresión extrínseca del bronquio principal derecho y tercio medio traqueal por cuerpos vertebrales torácicos. A su vez, tenía una disminución del diámetro anteroposterior del tórax, factor determinante en la aparición de los síntomas. Se intervino mediante fijación de vértebra torácica T3-T11, con posterior mejoría clínica y funcional respiratoria.La escoliosis asociada a alteración de función pulmonar y estridor debe hacer sospechar la existencia de compresión de la vía aérea, especialmente, en pacientes con reducción del diámetro anteroposterior del tóra

Idiopathic scoliosis is the abnormal flexion and rotation of the vertebral bodies, causing respiratory symptoms and altered pulmonary function. Straight back syndrome is a decreased in the anteroposterior diameter of the thorax. We present a 13-year-old patient with idiopathic scoliosis who developed progressive dyspnea, inspiratory stridor and a significant decrease in pulmonary function, because of extrinsic compression of the right main bronchus and the middle third of trachea by the thoracic vertebral bodies. She had also a decreased anteroposterior diameter of the thorax, being a determining factor in the appearance of symptoms. Surgery was performed by thoracic vertebra fixation T3 to T11, with subsequent clinical and functional respiratory improvement.Scoliosis associated with altered pulmonary function and stridor should make us suspect the existence of airway compression, especially in patients with reduction of the anteroposterior diameter of the thorax

[Bronchial hyperresponsiveness to methacholine in children under 4 years with recurrent bronchitis]. / Hiperrespuesta bronquial a la metacolina en niños menores de 4 años con bronquitis de repetición.

OBJECTIVE: To evaluate bronchial hyperresponsiveness in children under 4 years of age with recurrent wheezing bronchitis, and to determine if its presence or absence can predict the subsequent progression to a transient or persistent wheezing bronchitis phenotype. POPULATION AND METHODS: A bronchial challenge test was performed with methacholine using a modified tidal volume method, without sedation in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥ 5% or an increase in respiration rate of >50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress. RESULTS: A total of 63 patients and 16 controls were studied (mean age 23.9 vs. 25.2 months). The PCw was lower than the control group (≤ 4 mg/ml) in 43 (68%) children from the bronchitis group (P<0.001). No significant adverse effects were observed on performing the test. After a mean follow up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent and frequent wheezing (P=0.63). CONCLUSIONS: A high percentage of children under 4 years of age affected by wheezing bronchitis had a bronchial hyperresponse. The subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness.