Exhaled breath profiling using broadband quantum cascade laser-based spectroscopy in healthy children and children with asthma and cystic fibrosis.

Exhaled breath analysis is a potential non-invasive tool for diagnosing and monitoring airway diseases. Gas chromatography-mass spectrometry and electrochemical sensor arrays are the main techniques to detect volatile organic compounds (VOC) in exhaled breath. We developed a broadband quantum cascade laser spectroscopy technique for VOC detection and identification. The objective of this study was to assess the repeatability of exhaled breath profiling with broadband quantum cascade laser-based spectroscopy and to explore the clinical applicability by comparing exhaled breath samples from healthy children with those from children with asthma or cystic fibrosis (CF). Healthy children and children with stable asthma or stable CF, aged 6-18 years, were included. Two to four exhaled breath samples were collected in Tedlar bags and analyzed by quantum cascade laser spectroscopy to detect VOCs with an absorption profile in the wavenumber region between 832 and 1262.55 cm(-1). We included 35 healthy children, 39 children with asthma and 15 with CF. Exhaled breath VOC profiles showed poor repeatability (Spearman's rho = 0.36 to 0.46) and agreement of the complete profiles. However, we were able to discriminate healthy children from children with stable asthma or stable CF and identified VOCs that were responsible for this discrimination. Broadband quantum cascade laser-based spectroscopy detected differences in VOC profiles in exhaled breath samples between healthy children and children with asthma or CF. The combination of a relatively easy and fast method and the possibility of molecule identification makes broadband quantum cascade laser-based spectroscopy attractive to investigate the diagnostic and prognostic potential of volatiles in exhaled breath.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

Multicomponent gas analysis using broadband quantum cascade laser spectroscopy.

We present a broadband quantum cascade laser-based spectroscopic system covering the region between 850 and 1250 cm(-1). Its robust multipass cavity ensures a constant interaction length over the entire spectral region. The device enables the detection and identification of numerous molecules present in a complex gas mixture without any pre-treatment in two minutes. We demonstrate that we can detect sub-ppmv concentration of acetone in presence of 2% of water at the same wavenumber region.

Perinatal risk factors for wheezing phenotypes in the first 8 years of life.

BACKGROUND: A novel data-driven approach was used to identify wheezing phenotypes in pre-schoolchildren aged 0-8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes. OBJECTIVE: The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention. METHODS: In the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with 'never/infrequent wheeze' as reference category. RESULTS: Complete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day-care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy. CONCLUSION AND CLINICAL RELEVANCE: We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day-care attendance and breastfeeding, and may be important targets for prevention programmes.

Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms.

BACKGROUND: Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS). OBJECTIVES: To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life. METHODS: We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children. RESULTS: The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts. CONCLUSION: A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.

Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease.

Little is known about the etiology of childhood acute lymphoblastic leukemia (ALL). The presence of atopic disease has been shown to protect against developing childhood ALL. The aim of this study was to examine whether single nucleotide polymorphisms (SNPs) in innate immunity genes previously associated with atopic disease, can elucidate the inverse association between childhood ALL and atopic disease. We studied 525 children, including 192 with childhood ALL, 149 with atopic disease and 184 healthy control subjects. We compared genotype distributions of 29 SNPs in genes of TLR2, TLR4, TLR6, TLR9, TLR10 and CD14 between the three groups and corrected for multiple testing. The genotype distributions of two SNPs in the TLR6 gene, rs5743798 and rs6531666, differed significantly between children with ALL, children with atopic disease and control subjects. Particularly in children with atopic eczema, risk alleles for atopic disease were observed more often than in control subjects, and less often in children with ALL than in control subjects. These findings support the immune surveillance hypothesis as an explanation for the protective association of atopic disease on childhood ALL. Further investigation is warranted to examine in more detail the role of innate immunity in the development of childhood ALL.

Childhood diet and asthma and atopy at 8 years of age: the PIAMA birth cohort study.

Diet may affect the development of asthma. We investigated whether asthma or atopy outcomes at 8 yrs of age were associated with long-term dietary exposure, and whether associations were different for consumption at early or later age. The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort enrolled 4,146 participants at baseline, who were followed up to 8 yrs of age. Dietary intakes of interest were fruit, vegetables, brown/wholemeal bread, fish, milk, butter and margarine. Associations between food intake at early (2-3 yrs) and later (7-8 yrs) age, and long-term intake, asthma and atopy at 8 yrs of age were calculated by logistic regression. Complete longitudinal dietary data for at least one of the food groups were available for 2,870 children. Fruit consumption at early age was associated with reduced asthma symptoms (OR per 1 consumption day per week increase 0.93, 95% CI 0.85-1.00). Long-term fruit intake was inversely associated with asthma symptoms (OR 0.90, 95% CI 0.82-0.99) and sensitisation to inhaled allergens (OR 0.90, 95% CI 0.82-0.99). We found no consistent associations between diet and outcomes for other foods. This study indicates no consistent effects of increased early or late consumption, or long-term intake of certain foods on asthma and atopy in 8-yr-olds, with a possible exception for fruit.

Respiratory medicines for children: current evidence, unlicensed use and research priorities.

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.

Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness.

INTRODUCTION: ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV(1)) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. AIM: To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene-environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. METHODS: Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV(1) and BHR at age 8 years; asthma was based on questionnaire data at age 8. RESULTS: In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV(1)% predicted. CONCLUSIONS: We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Smoke exposure, airway symptoms and exhaled nitric oxide in infants: the Generation R study.

The effect of pre- and post-natal smoke exposure on exhaled nitric oxide fraction (F(eNO)) in infants was evaluated and the association between respiratory symptoms and F(eNO) in the first 2 months of life was investigated. The Generation R study is a population-based, prenatally recruited birth cohort. Exposures were assessed by means of questionnaires prospectively administered during pregnancy and after birth. Successful off-line F(eNO) measurements during tidal breathing were obtained in 187 infants (median age 6.9 weeks). The association between possible determinants and log F(eNO) was investigated with multiple linear regression analysis. Infants exposed pre- and post-natally to smoke showed lower F(eNO) than infants exposed only after birth (geometric mean difference (95% confidence interval) 1.5 (1.0-2.1) ppb) and never-exposed infants (1.4 (1.0-1.8) ppb). F(eNO) was reduced in infants with severe upper respiratory symptoms compared with infants with nonsevere symptoms (1.6 (1.0-2.4) ppb). Infants with symptoms of the lower respiratory tract had lower F(eNO) than asymptomatic infants (1.2 (1.0-1.50) ppb). In conclusion, the nature of the association between smoke exposure and exhaled nitric oxide fraction is dependent on timing and intensity of exposure. The occurrence and the severity of respiratory symptoms in the first 2 months of life are associated with lower exhaled nitric oxide fraction.

Exhaled nitric oxide in infants--what is a nice test like FENO doing in a place like this?

In adults and older children the measurement of fractional exhaled nitric oxide (FENO) has been shown to be useful as a tool to diagnose and monitor eosinophilic airway inflammation. However, the recommended method to measure FENO in school-age children is not suited for use in preschool children and infants. This article reviews the data on FENO measurements in infants. In the first year of life, measurement of FENO can be done during tidal breathing or during a single forced passive expiration. Several technical factors, including contamination with nasal and ambient NO, and the influence of expiratory flow influence FENO levels in infants. Because asthma is uncommon in infants and wheezing is often related to viral infections, considerable differences in clinical utility of FENO between older children and infants could be expected. From the available data FENO could potentially be useful to identify early-onset asthma, to diagnose primary ciliary dyskinesia (PCD), and to monitor the effect of various treatments. In conclusion, there is still much uncertainty about the potential clinical utility of FENO in infants. There is a need for clinical studies showing the merits and limitations of different methodologies, to standardize FENO measurements in infants, and to obtain normal reference values for this age group.

Nasal nitric oxide in cystic fibrosis with and without humming.

BACKGROUND: Nasal nitric oxide (nNO) values are reduced in patients with cystic fibrosis (CF). Humming during nNO measurement increases nNO values in healthy subjects. Nasal NO is reduced in patients with CF, sinus disease or nasal polyps. Humming nNO values have not been reported in CF patients yet. Our aim was to explore humming nNO values in CF patients and assess whether nNO during humming is a better discriminator than silent nNO measurements in this patient group. MATERIALS AND METHODS: In a cross sectional study we measured nNO concentrations in healthy controls (HC) and in CF patients (n = 23 and 31, respectively). The participants held their breath for 10 s while air was passively extracted from one nostril with 700 mL min(-1) for direct NO measurements (NIOX chemiluminescence analyser). Subsequently nNO was measured during humming with the mouth closed for 10 s. RESULTS: Mean nNO in parts per billion (p.p.b.) (SD) during breath hold was 499 (164) and 240 (139), respectively. The median nNO peak (p.p.b., minimum-maximum) during humming was 1500 (425-4100) for HC and 120 (23-500) for CF. There was a highly significant difference between nNO both with and without humming between CF and HC (P < 0.01). The sensitivity and specificity of nNO for detecting CF were better with humming. CONCLUSION: Nasal NO concentrations with and without humming are significantly decreased in CF. Humming nNO is an excellent discriminator between HC and CF and performs better than silent nNO.

Repeated measurements of mite and pet allergen levels in house dust over a time period of 8 years.

BACKGROUND: Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. OBJECTIVE: We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. RESULTS: Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. CONCLUSION: Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended.

Nasal NO measurement by direct sampling from the nose during breathhold: Aspiration flow, nasal resistance and reproducibility.

The objective of this study was assessment of the effect of aspiration flow, the nasal cycle, and time on nasal nitric oxide (nNO) concentrations in air sampled from one nostril during breathhold. nNO was measured in 45 healthy subjects (19 males, aged 18-45 years) from one nostril during breathholding. We compared nNO values and time to plateau in both nostrils with 3 aspiration flows (280, 700, 1,200 ml/min) and assessed the short-term and long-term reproducibility. Mean nNO values at flows of 280, 700 and 1,200 ml/min differed significantly (P < 0.01): 854, 474, 380 ppb, respectively. The (median) plateau was reached after 6, 4 and 3 s for the different flows. The within-subject coefficient of variability was always < 5%. We found no difference in nNO between left-, right-, largest or smallest nostril (P > 0.10). nNO values after 6, 24 h and 7 days were not significantly different from baseline (P > 0.10) and showed fair reproducibility. The highest aspiration flow was experienced as unpleasant. nNO can be measured in either nostril and shows no diurnal variation. The measurement is quick, reproducible, feasible and best accepted with an aspiration flow of 700 ml/min during breathhold for 10 s.

Nasal nitric oxide and nasal allergy.

Measurements of nasal nitric oxide (nNO) are attractive because they are completely noninvasive and can easily be performed. The measurements may be useful in the early diagnosis of patients with chronic airway disorders such as Kartager's syndrome and cystic fibrosis. The possible use of nNO measurements in the diagnosis and treatment of allergic rhinitis still needs to be further evaluated because of the variable and also contradicting findings of nNO concentrations in this disease. In this review we will discuss the origin, production and measurement of nNO as well as the effect of allergic rhinitis, nasal allergen challenge and medication on nNO. Subsequently, we examine published data on allergic rhinitis and nNO, and summarize the effect of treatment of rhinitis on nNO. Finally, we discuss the potential future role for nNO in the diagnosis and management of allergic rhinitis.

Gas cooking, kitchen ventilation, and asthma, allergic symptoms and sensitization in young children--the PIAMA study.

BACKGROUND: Several studies reported inconsistent associations between using gas for cooking and respiratory symptoms or lung function in children. Kitchen ventilation characteristics may modify the relationship between gas cooking and respiratory health. The aim of this study was to investigate the effect of kitchen ventilation (while cooking) on the relationship between gas cooking, combustion product dispersal, and respiratory and allergic outcomes in children. METHODS: Data on respiratory and allergic symptoms and diagnoses were collected by yearly questionnaires in a population of over 3000 children participating in a birth cohort study on development of allergy and asthma. At 4 years of age, a sub-sample of 647 children provided blood samples for antibody testing. Data on gas cooking and kitchen ventilation were collected when the children were 5 years old. Based on these data a model was constructed to determine the chance of accumulation of combustion products (CACP) in the kitchen. RESULTS: No relationship was found between gas cooking and any of the respiratory or allergy outcomes except nasal symptoms. The overall results did not change when the 'CACP' was used as exposure variable instead, while the association for nasal symptoms decreased to borderline significance. CONCLUSION: Our results suggest that gas cooking per se is associated with nasal symptoms in young children and not with the other respiratory symptoms that were investigated. Taking kitchen ventilation characteristics into account did not lead to different conclusions in this population where, according to the classification system, the majority of households using gas for cooking have insufficient kitchen ventilation.

Progression of lung disease on computed tomography and pulmonary function tests in children and adults with cystic fibrosis.

BACKGROUND: A study was undertaken to compare the ability of computed tomographic (CT) scores and pulmonary function tests to detect changes in lung disease in children and adults with cystic fibrosis (CF). METHODS: CT scans and pulmonary function tests were retrospectively studied in a cohort of patients with CF aged 5-52 years for whom two or three CT scans at 3 year intervals were available, together with pulmonary function test results. All CT scans were scored by two observers. Pulmonary function results were expressed as percentage predicted and Z scores. RESULTS: Of 119 patients studied, two CT scans were available in 92 patients and three in 24. CT (composite and component) scores and lung function both deteriorated significantly (p<0.02). Peripheral bronchiectasis worsened by 1.7% per year in children (p<0.0001) and by 1.5% per year in adults (p<0.0001). Bronchiectasis worsened in 68 of 92 patients while forced expiratory volume in 1 second (FEV1) worsened in 54 of 92 patients; bronchiectasis also deteriorated in 27 patients with stable or improving FEV1. The CT score (and its components) and pulmonary function tests showed similar rates of deterioration in adults and children (p>0.09). CONCLUSION: The peripheral bronchiectasis CT score deteriorates faster and more frequently than lung function parameters in children and adults with CF, which indicates that pulmonary function tests and CT scans measure different aspects of CF lung disease. Our data support previous findings that the peripheral bronchiectasis CT score has an added value to pulmonary function tests in monitoring CF lung disease.