NMR Profiling of Exhaled Breath Condensate Defines Different Metabolic Phenotypes of Non-Cystic Fibrosis Bronchiectasis.

Nuclear-magnetic-resonance (NMR) profiling of exhaled breath condensate (EBC) provides insights into the pathophysiology of bronchiectasis by identifying specific biomarkers. We evaluated whether NMR-based metabolomics discriminates the EBC-derived metabolic phenotypes ("metabotypes") of 41 patients with non-cystic fibrosis (nCF) bronchiectasis of various etiology [24 subjects with Primary Ciliary Dyskinesia (PCD); 17 patients with bronchiectasis not associated with PCD (nCF/nPCD)], who were compared to 17 healthy subjects (HS). NMR was used for EBC profiling, and Orthogonal Projections to Latent Structures with partial least-squares discriminant analysis (OPLS-DA) was used as a classifier. The results were validated by using the EBC from 17 PCD patients not included in the primary analysis. Different statistical models were built, which compared nCF/nPCD and HS, PCD and HS, all classes (nCF/nPCD-PCD-HS), and, finally, PCD and nCF/nPCD. In the PCD-nCF/nPCD model, four statistically significant metabolites were able to discriminate between the two groups, with only a minor reduction of the quality parameters. In particular, for nCF/nPCD, acetone/acetoin and methanol increased by 21% and 18%, respectively. In PCD patients, ethanol and lactate increased by 25% and 28%, respectively. They are all related to lung inflammation as methanol is found in the exhaled breath of lung cancer patients, acetone/acetoin produce toxic ROS that damage lung tissue in CF, and lactate is observed in acute inflammation. Interestingly, a high concentration of ethanol hampers cilia beating and can be associated with the genetic defect of PCD. Model validation with 17 PCD samples not included in the primary analysis correctly predicted all samples. Our results indicate that NMR of EBC discriminates nCF/nPCD and PCD bronchiectasis patients from HS, and patients with nCF/nPCD from those with PCD. The metabolites responsible for between-group separation identified specific metabotypes, which characterize bronchiectasis of a different etiology.

Advances in paediatrics in 2019: current practices and challenges in allergy, endocrinology, gastroenterology, public health, neonatology, nutrition, nephrology, neurology, respiratory diseases and rheumatic diseases.

We highlight the main developments that have been published during the first semester of the last year in the Italian Journal of Pediatrics. We have carefully chosen information from numerous exciting progresses issued in the Journal in the field of allergy, endocrinology, gastroenterology, neonatology, nutrition, nephrology, neurology, public health, respiratory diseases and rheumatic diseases. The impact on the care of patients has been placed in the broader context of studies that appeared in other journals. We think that many observations can be used directly to upgrade management of patients.

Amino acid-sesquiterpene lactone conjugates from the aerial parts of Centaurea pungens and evaluation of their antimicrobial activity.

Two new amino acid-sesquiterpene lactone conjugates, named centaureolide A (1) and centaureolide B (2) along with a germacrane derivative (3), five flavonoids (4-8) and one quinic acid derivative (9) have been isolated from the aerial parts of Centaurea pungens (Asteraceae). Their structures were established by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. The never reported sesquiterpene lactones have been determined as germacrane derivatives (1 and 2) characterized by the unusual occurrence of a proline moiety. In order to validate the use of the extract of C. pungens in folk medicine, the antimicrobial activity of the isolated compounds against the Gram-positive strains Bacillus cereus, Staphylococcus aureus and Listeria innocua and the Gram-negative strains Pseudomonas aeruginosa and Pseudomonas fragi was evaluated.

Asthma: Differential Diagnosis and Comorbidities.

Childhood asthma remains a multifactorial disease with heterogeneous clinical phenotype and complex genetic inheritance. The primary aim of asthma management is to achieve control of symptoms, in order to reduce the risk of future exacerbations and progressive loss of lung function, which results especially challenging in patients with difficult asthma. When asthma does not respond to maintenance treatment, firstly, the correct diagnosis needs to be confirmed and other diagnosis, such as cystic fibrosis, primary ciliary dyskinesia, immunodeficiency conditions or airway and vascular malformations need to be excluded. If control remains poor after diagnostic confirmation, detailed assessments of the reasons for asthma being difficult-to-control are needed. Moreover, all possible risk factors or comorbidities (gastroesophageal reflux, rhinosinusitis, dysfunctional breathing and/or vocal cord dysfunction, obstructive sleep apnea and obesity) should be investigated. At the same time, the possible reasons for poor symptom control need to be find in all modifiable factors which need to be carefully assessed. Non-adherence to medication or inadequate inhalation technique, persistent environmental exposures and psychosocial factors are, currently, recognized as the more common modifiable factors. Based on these premises, investigation and management of asthma require specialist multidisciplinary expertise and a systematic approach to characterizing patients' asthma phenotypes and delivering individualized care. Moreover, since early wheezers are at higher risk of developing asthma, we speculate that precocious interventions aimed at early diagnosis and prevention of modifiable factors might affect the age at onset of wheezing, reduce the prevalence of persistent later asthma and determine long term benefits for lung health.

Respiratory syncytial virus prophylaxis and the "special population".

Bronchiolitis is the most frequent airway infection in the first 2 years of life, and the respiratory syncytial virus (RSV) is the most frequently responsible virus. In selected high-risk groups, RSV may cause severe respiratory disease leading to hospitalization, need for mechanical ventilation, and even death. These high-risk groups include children with congenital heart disease, infants with neuromuscular impairment, cystic fibrosis, Down Syndrome, immunodeficiency syndromes and others specific conditions. In these high-risk populations defined in literature as "special population", a 3- to 10-fold increase in the rate of RSV hospitalization has been observed, justifying RSV specific prophylaxis with palivizumab, a monoclonal antibody that binds a viral glycoprotein epitope and blocks the link between RSV and target cell. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomized clinical trials are not feasible. The purpose of this paper is to give an update from the literature of various conditions at higher risk to develop severe RSV infection, and to offer an overview of the efficacy of palivizumab in preventing RSV infection in these specific populations.

Pediatric severe asthma: a case series report and perspectives on anti-IgE treatment.

BACKGROUND: The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly "severe therapy-resistant" asthmatics by a proper filtering process. Herein we report on four cases diagnosed as difficult asthma, detail the workup that resulted in the ultimate diagnosis, and provide the process that led to the prescription of omalizumab. CASE PRESENTATION: All children had been initially referred because of asthma not responding to long-term treatment with high-dose inhaled steroids, long-acting ß2-agonists and leukotriene receptor antagonists. Definitive diagnosis was severe asthma. Three out four patients were treated with omalizumab, which improved asthma control and patients' quality of life. We reviewed the current literature on the diagnostic approach to the disease and on the comorbidities associated with difficult asthma and presented the perspectives on omalizumab treatment in children and adolescents. Based on the evidence from the literature review, we also proposed an algorithm for the diagnosis of pediatric difficult-to-treat and severe asthma. CONCLUSIONS: The management of asthma is becoming much more patient-specific, as more and more is learned about the biology behind the development and progression of asthma. The addition of omalizumab, the first targeted biological treatment approved for asthma, has led to renewed optimism in the management of children and adolescents with atopic severe asthma.

Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies.

Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities. Most patients report a daily year-round wet cough or nose congestion starting in the first year of life. Daily wet cough, associated with recurrent infections exacerbations, results in the development of chronic suppurative lung disease, with localized-to-diffuse bronchiectasis. No diagnostic test is perfect for confirming PCD. Diagnosis can be challenging and relies on a combination of clinical data, nasal nitric oxide levels plus cilia ultrastructure and function analysis. Adjunctive tests include genetic analysis and repeated tests in ciliary culture specimens. There are currently 33 known genes associated with PCD and correlations between genotype and ultrastructural defects have been increasingly demonstrated. Comprehensive genetic testing may hopefully screen young infants before symptoms occur, thus improving survival. Recent surprising advances in PCD genetic designed a novel approach called "gene editing" to restore gene function and normalize ciliary motility, opening up new avenues for treating PCD. Currently, there are no data from randomized clinical trials to support any specific treatment, thus, management strategies are usually extrapolated from cystic fibrosis. The goal of treatment is to prevent exacerbations, slowing the progression of lung disease. The therapeutic mainstay includes airway clearance maneuvers mainly with nebulized hypertonic saline and chest physiotherapy, and prompt and aggressive administration of antibiotics. Standardized care at specialized centers using a multidisciplinary approach that imposes surveillance of lung function and of airway biofilm composition likely improves patients' outcome. Pediatricians, neonatologists, pulmonologists, and ENT surgeons should maintain high awareness of PCD and refer patients to the specialized center before sustained irreversible lung damage develops. The recent creation of a network of PCD clinical centers, focusing on improving diagnosis and treatment, will hopefully help to improve care and knowledge of PCD patients.

Longitudinal Follow-up of Chronic Pulmonary Manifestations in Esophageal Atresia: A Clinical Algorithm and Review of the Literature.

In the past decades improved surgical techniques and better neonatal supportive care have resulted in reduced mortality of patients with esophageal atresia (EA), with or without tracheoesophageal fistula, and in increased prevalence of long-term complications, especially respiratory manifestations. This integrative review describes the techniques currently used in the pediatric clinical practice for assessing EA-related respiratory disease. We also present a novel algorithm for the evaluation and surveillance of lung disease in EA. A total of 2813 articles were identified, of which 1451 duplicates were removed, and 1330 were excluded based on review of titles and abstracts. A total of 32 articles were assessed for eligibility. Six reviews were excluded, and 26 original studies were assessed. Lower respiratory tract infection seems frequent, especially in the first years of life. Chronic asthma, productive cough, and recurrent bronchitis are the most common respiratory complaints. Restrictive lung disease is generally reported to prevail over the obstructive or mixed patterns, and, overall, bronchial hyperresponsiveness can affect up to 78% of patients. At lung imaging, few studies detected bronchiectasis and irregular cross-sectional shape of the trachea, whereas diffuse bronchial thickening, consolidations, and pleural abnormalities were the main chest X-ray findings. Airway endoscopy is seldom included in the available studies, with tracheomalacia and tracheobronchial inflammation being described in a variable proportion of cases. A complete diagnostic approach to long-term respiratory complications after EA is mandatory. In the presence of moderate-to-severe airway disease, patients should undergo regular tertiary care follow-up with functional assessment and advanced chest imaging.

Progress in pediatrics in 2015: choices in allergy, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, nephrology, neurology, nutrition, oncology and pulmonology.

This review focuses key advances in different pediatric fields that were published in Italian Journal of Pediatrics and in international journals in 2015. Weaning studies continue to show promise for preventing food allergy. New diagnostic tools are available for identifying the allergic origin of allergic-like symptoms. Advances have been reported in obesity, short stature and autoimmune endocrine disorders. New molecules are offered to reduce weight gain and insulin-resistance in obese children. Regional investigations may provide suggestions for preventing short stature. Epidemiological studies have evidenced the high incidence of Graves' disease and Hashimoto's thyroiditis in patients with Down syndrome. Documentation of novel risk factors for celiac disease are of use to develop strategies for prevention in the population at-risk. Diagnostic criteria for non-celiac gluten sensitivity have been reported. Negative effect on nervous system development of the supernumerary X chromosome in Klinefelter syndrome has emerged. Improvements have been made in understanding rare diseases such as Rubinstein-Taybi syndrome. Eltrombopag is an effective therapy for immune trombocytopenia. Children with sickle-cell anemia are at risk for nocturnal enuresis. Invasive diseases caused by Streptococcus pyogenes are still common despite of vaccination. No difference in frequency of antibiotic prescriptions for acute otitis media between before the publication of the national guideline and after has been found. The importance of timing of iron administration in low birth weight infants, the effect of probiotics for preventing necrotising enterocolitis and perspectives for managing jaundice and cholestasis in neonates have been highlighted. New strategies have been developed to reduce the risk for relapse in nephrotic syndrome including prednisolone during upper respiratory infection. Insights into the pathophysiology of cerebral palsy, arterial ischemic stroke and acute encephalitis may drive advances in treatment. Recommendations on breastfeeding and complementary feeding have been updated. Novel treatments for rhabdomyosarcoma should be considered for paediatric patients. Control of risk factors for bronchiolitis and administration of pavilizumab for preventing respiratory syncytial virus infection may reduce hospitalization. Identification of risk factors for hospitalization in children with wheezing can improve the management of this disease. Deletions or mutations in genes encoding proteins for surfactant function may cause diffuse lung disease.

DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes.

Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)-left-right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.

Hypovitaminosis D: a novel finding in primary ciliary dyskinesia.

BACKGROUND: A relationship between low levels of serum vitamin D and respiratory infections has been established. No study has examined the frequency and clinical relevance of vitamin D deficiency in patients with primary ciliary dyskinesia (PCD). METHODS: Vitamin D levels were measured in 22 PCD patients (7 females, 10.5 years, range, 2-34 years). In PCD, pulmonary function tests (PFTs), sputum microbiology, self-reported physical activity (PA) level, and quality of life (QoL) by means of the Saint George's Respiratory Questionnaire (SGRQ), were also assessed. RESULTS: Seventy-two percent of PCD patients were vitamin-D deficient-to-insufficient and 28% were sufficient. No differences in PFTs parameters were found between vitamin D deficiency-to-insufficiency and sufficiency groups. Patients with vitamin D deficiency-to-insufficiency had significantly higher SGRQ total scores, and thus poorer QoL (p = 0.03). Seventy-nine percent of PCD subjects had limitations in performing vigorous activities, and 53% performed less than 3 hours of PA per week. Vitamin D deficiency-to-insufficiency and sufficiency groups did not show any differences in age at PCD diagnosis or at onset of respiratory symptoms, BMI, atopy, current asthma or bronchiectasis. However, 79% of patients with bronchiectasis had vitamin D deficiency-to-insufficiency. No differences were found in the rate of positive sputum cultures and in the number of antibiotic courses between the two groups. CONCLUSIONS: Hypovitaminosis D is common in PCD patients, and is associated with poorer QoL. We recommend the assessment and treatment of hypovitaminosis D to be included in the routine management of PCD.

Progress in pediatrics in 2013: choices in allergology, endocrinology, gastroenterology, hypertension, infectious diseases, neonatology, neurology, nutrition and respiratory tract illnesses.

This review will provide new information related to pathophysiology and management of specific diseases that have been addressed by selected articles published in the Italian Journal of Pediatrics in 2013, focusing on allergology, endocrinology, gastroenterology, hypertension, infectious diseases, neonatology, neurology, nutrition and respiratory tract illnesses in children. Recommendations for interpretation of skin prick test to foods in atopic eczema, management of allergic conjunctivitis, hypertension and breastfeeding in women treated with antiepileptic drugs and healthy breakfast have been reported. Epidemiological studies have given emphasis to high incidence of autoimmune disorders in patients with Turner syndrome, increasing prevalence of celiac disease, frequency of hypertension in adolescents, incidence and risk factor for retinopathy of prematurity. Advances in prevention include elucidation of the role of probiotics in reducing occurrence of allergies and feeding intolerance, and events of foetal life that influence later onset of diseases. Mechanistic studies suggested a role for vitamin D deficiency in asthma and type 1 diabetes and for reactivation of Varicella-Zoster virus in aseptic meningitis. Regarding diagnosis, a new mean for the diagnosis of hyperbilirubinaemia in newborns, a score for recognition of impaired nutritional status and growth and criteria for early Dyke-Davidoff-Masson Syndrome have been suggested. New therapeutic approaches consist of use of etanercept for reducing insulin dose in type 1 diabetes, probiotics in atopic eczema, and melatonin in viral infections.

Sleep disordered breathing and airway disease in primary ciliary dyskinesia.

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) may develop in primary ciliary dyskinesia (PCD), leading to these diseases worsening one another. METHODS: Sixteen stable PCD patients (4.9-17.2 years) and 42 controls underwent overnight respiratory polysomnography (rPSG) and Sleep Disturbances Scale for Children (SDSC). In PCD we assessed nasal endoscopy, pulmonary function tests and chest high-resolution computed tomography (HRCT). RESULTS: Compared with controls, PCD had higher obstructive apnoea (4.7 vs 0.2, P < 0.001), central apnoea (0.8 vs 0.2, P < 0.001), hypopnoea (1.8 vs 0.2, P < 0.001), apnoea-hypopnoea (7.8 vs 0.6, P < 0.001), oxygen desaturation indexes (ODI; 0.7 vs 0.2, P = 0.002), and mean oxygen desaturation (4% vs 1%, P < 0.001), while mean and nadir oxygen saturation (97.1% vs 98.1, P < 0.001) (93% vs 97.2%, P < 0.001) were lower, respectively. In PCD, SDSC was unrelated to rPSG (P > 0.05), with total score and subscores of disorders in initiating and maintaining sleep, and sleep-wake transition lower than controls. PCD patients had chronic rhinosinusitis (100%) and adenoidal hypertrophy (50%). Total HRCT score was 7 (range 0-14). ODI correlated with functional residual capacity (r = 0.8, P = 0.02), total HRCT (r = 0.6, P = 0.03) and peribronchial thickening scores (r = 0.7, P = 0.02). Oxygen saturation was associated with bronchiectasis severity score (r = -0.6, P = 0.02). CONCLUSIONS: PCD's parents may underestimate SDB. As nocturnal desaturation is associated with lung function and structure abnormalities, SDB may significantly contribute to pulmonary morbidity.

Respiratory manifestations in patients with inherited metabolic diseases.

Growing evidence indicates that inherited metabolic diseases are increasingly being recognised. Life expectancy for many patients is progressively improving because new therapeutic strategies are available. Because most inherited metabolic diseases are systemic disorders, virtually all organs may be involved. Respiratory disease complicates the management of several inherited metabolic diseases, either at presentation or as late-onset features. This review will describe the most exemplary respiratory manifestations of inherited metabolic diseases in childhood and adulthood. Since airways disease worsens the morbidity of many inherited metabolic disorders, leading to increased hospitalisations, mortality and overall healthcare costs, respiratory manifestations of inherited metabolic diseases need to be carefully recognised and treated. All patients with inherited metabolic disease and suspected airway disease should undergo a detailed diagnostic work-up. Current treatments for several inherited metabolic diseases (including enzyme replacement therapy, substrate reduction, bone marrow transplantation, or even more innovative strategies such as pharmacological chaperone or gene therapies) may provide significant benefits for associated respiratory disease. The integration of several specialists dedicated to airway disease management in a multidisciplinary team is essential to provide the most appropriate care to children and adults with inherited metabolic disease.

What drives prescribing of asthma medication to preschool wheezing children? A primary care study.

There is limited information on which data primary care pediatricians (PCPs) use to decide whether to prescribe or not asthma maintenance treatment, and what drives prescribing a specific therapy. The study aim was to investigate how prescribing anti-asthma maintenance treatment to preschool wheezing children is influenced by patient, family, environmental, and PCP characteristics. We conducted a cross-sectional study at 32 PCPs sites in Campania, Italy. Medical, family, and environmental information of 376 preschool wheezy children, and characteristics of the enrolled PCPs were collected. Main outcome measures of multilevel multivariate logistic regression analyses were the prescribing of maintenance treatment, and the prescription of a combined therapy as opposed to monotherapy. Variables significantly associated with long-term inhaled corticosteroids (ICS) and/or leukotriene modifiers prescription included frequent wheezing (OR = 7.19), emergency department (ED) visits (OR = 2.21), personal allergic diseases (OR = 8.49), day-care/kindergarten attendance (OR = 2.67), a high PCP prescribing volume (OR = 2.74), and a low proportion of 0- to 5-year-old patients with wheezing diagnosis (OR = 1.16). Leukotriene modifiers plus ICS were much more likely prescribed than ICS or leukotriene modifiers alone to older children (OR = 1.06) and to patients experiencing frequent wheezing (OR = 3.00), ED visits (OR = 3.12), or tobacco smoke exposure during the first 2 years of life (OR = 2.04). Finally, PCP's characteristics significantly associated with ICS plus leukotriene modifiers prescription were group practice (OR = 4.16) and a high prescribing volume (OR = 1.45). Our findings suggest that child characteristics alone are not sufficient to explain how PCPs decide to prescribe maintenance treatment and which therapy to assign, but variables associated to PCPs are crucial as well.

Hyper IgM syndrome presenting as chronic suppurative lung disease.

The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination. Affected patients show humoral immunodeficiency and high susceptibility to opportunistic infections. Elevated serum IgM levels are the hallmark of the disease, even though in few rare cases they may be in the normal range. Hyper IgM is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some cases, alterations in different genes may be identified. Mutations in five genes have so far been associated to the disease, which can be inherited with an X-linked (CD40 ligand, and nuclear factor-kB essential modulator defects) or an autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA glycosylase mutation) pattern. The patient herein described presented with recurrent upper and lower respiratory infections and evidence of suppurative lung disease at the conventional chest imaging. The presence of low serum IgG and IgA levels, elevated IgM levels, and a marked reduction of in vivo switched memory B cells led to a clinical and functional diagnosis of HIGM although the genetic cause was not identified.

Cardiopulmonary assessment in primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare, usually autosomal recessive disorder of ciliary dysfunction associated with lung involvement, which has a great impact on health. There is limited information concerning the aerobic fitness of children and adolescents with PCD. The aim of this study was to assess cardiopulmonary functional capacity and its relationship with pulmonary function and physical activity (PA) levels in patients with PCD. DESIGN: Ten patients with PCD (age 13·2 ± 2·8 years) underwent spirometry and cardiopulmonary exercise testing. PA was investigated through a questionnaire. Eight age- and body mass index-matched healthy children were enrolled as controls. Main variables were forced expiratory volume at 1 s, peak oxygen uptake (VO(2peak) ) and time spent in PA. RESULTS: Forty per cent of patients with PCD had impaired lung function as expressed by FEV(1) < 85% predicted. Only patients with impaired lung function exhibited reduced VO(2peak) (18·1 ± 7·9 mL/kg/min). Time spent in total daily PA was slightly lower in patients than controls, with no difference between patients with normal or reduced lung function. In multiple regression models, male gender (ß = 0·518, P = 0·018), age (ß = 0·752, P = 0·035) and time spent in vigorous PA (ß = 0·353, P = 0·049) were independent predictors of aerobic fitness. CONCLUSIONS: Assessment of resting pulmonary function and cardiopulmonary functional capacity could contribute to the evaluation of pulmonary impairment in PCD. Given the benefit of physical exercise on airway clearance and on general health and quality of life, patients with PCD should be encouraged to adopt an active lifestyle.