Exercise Performance and Dynamic Hyperinflation in Lymphangioleiomyomatosis

Rationale: Lymphangioleiomyomatosis (LAM) is characterized by exercise performance impairment. Although airflow limitation is common, no previous studies have evaluated the prevalence and impact of dynamic hyperinflation (DH) in LAM. Objectives: To investigate the dynamic responses during maximal exercise and the prevalence, predictors, and repercussions of DH in LAM. Methods: Forty-two patients with LAM performed symptom-limited incremental cycle exercise and pulmonary functions tests (PFTs) and were compared with 10 age-matched healthy women. Dyspnea intensity, inspiratory capacity, oxygen saturation, and cardiac, metabolic, and respiratory variables were assessed during exercise. Patients with LAM also performed a 6-minute walk test (6MWT). Measurements and Main Results: Patients with LAM had higher baseline dyspnea, poorer quality of life, obstructive pattern, air trapping, and reduced diffusing capacity of carbon monoxide in PFTs. Although they had the same level of regular physical activity, their maximal exercise performance was reduced and was associated with ventilatory limitation, greater desaturation, and dyspnea. The prevalence of DH was high in LAM (55%), even in patients with mild spirometric abnormalities, and was correlated with airflow obstruction, air trapping, and diffusing capacity of carbon monoxide. Compared with the non-DH subgroup, the patients who developed DH had a ventilatory limitation contributing to exercise cessation on cycling and higher desaturation and dyspnea intensity during the 6MWT. Conclusions: Ventilatory limitation and gas exchange impairment are important causes of exercise limitation in LAM. DH is frequent in LAM, even in patients with mild spirometric abnormalities. DH was associated with the severity of disease, higher dyspnea, and lower oxygen saturation. In the 6MWT, desaturation and dyspnea were greater in patients with DH.

Respiratory physiotherapy can increase lower esophageal sphincter pressure in GERD patients

Background: Inspiratory muscle training (IMT) has been shown to increase diaphragm thickness. We evaluated the effect of IMT on mid-respiratory pressure (MRP) in patients with gastroesophageal reflux disease (GERD) and hypotensive lower esophageal sphincter (LES), and compared the results with a sham group. Methods: Twenty consecutive patients (progressive loading group) and 9 controls (sham group) were included. All patients had end expiratory pressure (EEP) between 5 and 10 mmHg, underwent esophageal manometry and pulmonary function tests before and after 8 weeks of training, and used a threshold IMT twice daily. The threshold IMT was set at 30% of the maximal inspiratory pressure for the progressive loading group; while, the threshold for sham-treated patients was set at 7 cmH(2)O for the whole period. Results: There was an increase in MRP in 15 (75%) patients in the progressive loading group, with an average gain of 46.6% (p<0.01), and in six (66%) patients in the sham group with a mean increase of 26.2% (p<0.01). However, there was no significant difference between the groups (p = 0.507). The EEP also increased compared with measurements before training (p<0.01), but it did not differ between groups (p = 0.727). Conclusion: IMT increased LES pressure in patients with GERD, in both the treatment and sham groups, after an eight-week program. Although there was no statistically significant difference between groups, suggesting the pressure increase in LES occurs regardless of the resistance load of the threshold IMT. These findings need to be confirmed in further studies with a larger sample. Registration number: 0922/09. (C) 2012 Elsevier Ltd. All rights reserved.

Physical Activity In Daily Life In Brazilian COPD Patients During and After Exacerbation

Background: Although hospitalization is recognized as an important cause of reduction in physical activity in daily life (PADL) in COPD, there is only one study evaluating this effect, and it was performed in European COPD patients who have a lower PADL than that of South American COPD patients. Objectives: To investigate the effect of hospitalization due to acute exacerbation of PADL in Brazilian COPD patients and to evaluate the factors that determines the physical activity levels during hospitalization and after discharge. Methods: PADL was quantified using a 3-axis accelerometer on the 3rd day of hospitalization and 1 month after discharge in Brazilian COPD patients who were hospitalized due to disease exacerbation. Six-minute walking distance (6MWD), lower limb strength and pulmonary function were also evaluated. Results: A total of 20 patients completed the study. During hospitalization, patients spent most of the time (87%) lying down or sitting; however, 1 month after they were walking >40 min/day. In addition, patients with prior hospitalization had a lower level of physical activity compared to those without a previous history of hospitalization. The time spent walking during hospitalization was significantly explained by the quadriceps strength (r(2) = 0.29; p < 0.05), while 1 month after, the time spent walking was only significantly explained by the 6MWD (r(2) = 0.51; p = 0.02). Conclusions: Brazilian COPD patients are inactive during hospitalization but become active 1 month after discharge. Previously hospitalized are more inactive both during and after exacerbation. The quadriceps strength and 6MWD explain the physical activity levels during hospitalization and at home, respectively.

Occurrence of asthma symptoms and of airflow obstruction in amateur swimmers between 8 and 17 years of age

Objective: To determine the prevalence of asthma symptoms and of airflow obstruction in amateur swimmers between 8 and 17 years of age, as well as to assess the awareness of asthma and asthma management among these swimmers, their parents, and their coaches. Methods: Our sample comprised 1,116 amateur swimmers who completed a modified version of the International Study of Asthma and Allergies in Childhood written questionnaire, to which questions regarding the reasons to initiate swimming and regarding asthma management had been added. In addition, the participants underwent spirometry prior to a swimming competition. Results: The prevalence of asthma symptoms in the last 12 months was 11.5%, and 327 (29.4%) of the participants reported "wheezing or whistling" in the past. Of the 223 swimmers who reported "asthma ever" or "bronchitis ever", only 102 (45.7%) reported having ever been treated: the most common "treatment" was swimming (in 37.3%), and only 12.7% used inhaled corticosteroids. Of the 254 participants (22.7%) with airflow obstruction, only 52 (20.5%) reported having asthma symptoms. Conclusions: Asthma symptoms are present in amateur swimmers, and a considerable number of such swimmers have airflow obstruction without symptoms. It is therefore likely that the prevalence of asthma is underestimated in this population. It is worrisome that, in our study sample, the swimmers previously diagnosed with asthma were not using the recommended treatments for asthma. The clinical implications of these findings underscore the importance of implementing educational measures for amateur swimmers, as well as for their parents and coaches, to help them recognize asthma symptoms and the consequent risks in the sports environment, in order to allow prompt diagnosis and early clinical intervention.

Exercise-induced bronchoconstriction in elite long-distance runners in Brazil

Objective: To determine the prevalence of exercise-induced bronchoconstriction among elite long-distance runners in Brazil and whether there is a difference in the training loads among athletes with and without exercise-induced bronchoconstriction. Methods: This was a cross-sectional study involving elite long-distance runners with neither current asthma symptoms nor a diagnosis of exercise-induced bronchoconstriction. All of the participants underwent eucapnic voluntary hyperpnea challenge and maximal cardiopulmonary exercise tests, as well as completing questionnaires regarding asthma symptoms and physical activity, in order to monitor their weekly training load. Results: Among the 86 male athletes recruited, participation in the study was agreed to by 20, of whom 5 (25%) were subsequently diagnosed with exercise-induced bronchoconstriction. There were no differences between the athletes with and without exercise-induced bronchoconstriction regarding anthropometric characteristics, peak oxygen consumption, baseline pulmonary function values, or reported asthma symptoms. The weekly training load was significantly lower among those with exercise-induced bronchoconstriction than among those without. Conclusions: In this sample of long-distance runners in Brazil, the prevalence of exercise-induced bronchoconstriction was high.

Modulation of Lung Allergic Response by Renal Ischemia and Reperfusion Injury

The Th1/Th2 balance represents an important factor in the pathogenesis of renal ischemia-reperfusion injury (IRI). In addition, IRI causes a systemic inflammation that can affect other tissues, such as the lungs. To investigate the ability of renal IRI to modulate pulmonary function in a specific model of allergic inflammation, C57Bl/6 mice were immunized with ovalbumin/albumen on days 0 and 7 and challenged with an ovalbumin (OA) aerosol on days 14 and 21. After 24 h of the second antigen challenge, the animals were subjected to 45 minutes of ischemia. After 24 h of reperfusion, the bronchoalveolar lavage (BAL) fluid, blood and lung tissue were collected for analysis. Serum creatinine levels increased in both allergic and non-immunized animals subjected to IRI. However, BAL analysis showed a reduction in the total cells (46%) and neutrophils (58%) compared with control allergic animals not submitted to IRI. In addition, OA challenge induced the phosphorylation of ERK and Akt and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung homogenates. After renal IRI, the phosphorylation of ERK and expression of COX-2 and iNOS were markedly reduced; however, there was no difference in the phosphorylation of Akt between sham and ischemic OA-challenged animals. Mucus production was also reduced in allergic mice after renal IRI. IL-4, IL-5 and IL-13 were markedly down-regulated in immunized/challenged mice subjected to IRI. These results suggest that renal IRI can modulate lung allergic inflammation, probably by altering the Th1/Th2 balance and, at least in part, by changing cellular signal transduction factors. Copyright (C) 2012 S. Karger AG, Basel

Spirometric values in elderly asthmatic patients are not influenced by obesity

Background Studies have suggested that asthma in obese individuals differs from the classic asthma phenotype, presenting as a disease that is more difficult to control. Objective The objective of the present study was to determine whether obesity, age or a combination of the two are associated with worse spirometry parameters in patients with asthma. Methods This was an observational cross-sectional study involving patients over 18 years of age who had been diagnosed with asthma (allergic or nonallergic). We evaluated the results of their spirometric tests. The patients were classified in accordance with two criteria: body mass index (BMI) and age. Based on their BMIs, the patients were divided into three groups: normal weight, overweight and obese. Patients were also separated into two categories by age: 18-59 years of age; and >= 60 years of age. Results We evaluated 451 patients with asthma and their spirometry tests. In the present study, the pulmonary function parameters were negatively correlated with BMI and age (P < 0.05). We found that there was a statistically significant correlation between spirometric values and BMI among patients 18-59 years of age (P < 0.001), however, among patients over 60, we did not observe this negative association. Conclusions and Clinical Relevance The spirometric values decreased significantly in proportion to the increase of BMI and age in patients with asthma, especially among young adults. There was no negative correlation between BMI and FEV1 in the group >= 60 years of age, suggesting that perhaps the time of disease is a major factor in the loss of lung function than weight gain in the elderly.

Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. Copyright (C) 2011 S. Karger AG, Basel

Influence of chest wall on lung mechanics during inspiration

RATIONALE: The interaction between lungs and chest wall influences lung volume, that determines lung history during respiration cycle. In this study, the influence of chest wall mechanics on respiratory system is assessed by the evaluation of inspiration pressure-volume curve (PV curve) under three different situations: closed-chest, open-chest and isolated lung. The PV curve parameters in each situation allow us to further understand the role played by different chest wall elements in the respiratory function. Methods: Twenty-four male Wistar rats (236 ± 29 g) were used. The animals were weighted and then anesthetized with xylazine 2% (O,SmL/kg) and ketamine 10% (0,9mL/kg), exsanguinated and later tracheostomies with a metallic cannula (14 gauge).The cannula was connected to an automatic small animal insufflator. This setup was connected to a pressure transducer (32 samples/s). The 24 animals were randomly separated in three groups:(i) closed chest,(ii) open chest and (iii) isolated lung. The rats were insufflated with 20mL quasi-statically (constant speed of 0,1mUs). lnsufflated volume and measured pressure data were kept and PV curves were obtained for all animals. The PV curves were fitted (non-linear least squares) against the sigmoid equation (1) to obtain the sigmoid equation parameters (a,b,c,d). Elastance measurements were obtained from linear regression of pressure/volume measurements in a 0,8s interval before and after the calculated point. Results: The parameters a,b and c showed no significant change, but the parameter d showed a significant variation among the three groups. The initial elastance also varied between open and closed chest, indicating the need of a higher pressure for the lung expansion, as can be seen in Table 1. Conclusion: A supporting effect of the chest wall was observed at the initial moments of inspiration, observed as a higher initial elastance in open chest situations than in closed chest situations (p=0,00001). The similar initial elastance for the isolated lung and closed chest may be explained by the specific method used for the isolated lung experiment. As the isolated lung is supported by the trachea vertically, the weight of the tissue may have a similar effect of the residual negative pressure in the thorax, responsible for maintaining the residual volume.

Outcome respiratorio a lungo termine nei soggetti affetti da cardiopatia congenita sottoposti ad intervento cardiochirurgico

Introduction: In the last years cardiac surgery for congenital heart disease (CHD) reduced dramatically mortality modifying prognosis, but, at the same time, increased morbidity in this patient population. Respiratory and cardiovascular systems are strictly anatomically and functionally connected, so that alterations of pulmonary hemodynamic conditions modify respiratory function. While very short-term alterations of respiratory mechanics after surgery were investigated by many authors, not as much works focused on long-term changes. In these subjects rest respiratory function may be limited by several factor: CHD itself (fetal pulmonary perfusion influences vascular and alveolar development), extracorporeal circulation (CEC), thoracotomy and/or sternotomy, rib and sternal contusions, pleural adhesions and pleural fibrosis, secondary to surgical injury. Moreover inflammatory cascade, triggered by CEC, can cause endothelial damage and compromise gas exchange. Aims: The project was conceived to 1) determine severity of respiratory functional impairement in different CHD undergone to surgical correction/palliation; 2) identify the most and the least CHD involved by pulmonary impairement; 3) find a correlation between a specific hemodynamic condition and functional anomaly, and 4) between rest respiratory function and cardiopulmonary exercise test. Materials and methods: We studied 113 subjects with CHD undergone to surgery, and distinguished by group in accord to pulmonary blood flow (group 0: 28 pts with normal pulmonary flow; group 1: 22 pts with increased flow; group 2: 43 pts with decreased flow; group 3: 20 pts with total cavo-pulmonary anastomosis-TCPC) followed by the Pediatric Cardiology and Cardiac Surgery Unit, and we compare them to 37 age- and sex-matched healthy subjects. In Pediatric Pulmonology Unit all pts performed respiratory function tests (static and dynamic volumes, flow/volume curve, airway resistances-raw- and conductance-gaw-, lung diffusion of CO-DLCO- and DLCO/alveolar volume), and CHD pts the same day had cardiopulmonary test. They all were examined and had allergological tests, and respiratory medical history. Results: restrictive pattern (measured on total lung capacity-TLC- and vital capacity-VC) was in all CHD groups, and up to 45% in group 2 and 3. Comparing all groups, we found a significant difference in TLC between healthy and group 2 (p=0.001) and 3 (p=0.004), and in VC between group 2 and healthy (p=0.001) and group 1(p=0.034). Inspiratory capacity (IC) was decreased in group 2 related to healthy (p<0.001) and group 1 (p=0.037). We showed a direct correlation between TLC and VC with age at surgery (p=0.01) and inverse with number of surgical interventions (p=0.03). Reduced FEV1/FVC ratio, Gaw and increased Raw were mostly present in group 3. DLCO was impaired in all groups, but up to 80% in group 3 and 50% in group 2; when corrected for alveolar volume (DLCO/VA) reduction persisted in group 3 (20%), 2 (6.2%) and 0 (7.1%). Exercise test was impaired in all groups: VO2max and VE markedly reduced in all but especially in group 3, and VE/VCO2 slope, marker of ventilatory response to exercise, is increased (<36) in 62.5% of group 3, where other pts had anyway value>32. Comparing group 3 and 2, the most involved categories, we found difference in VO2max and VE/VCO2 slope (respectively p=0.02 and p<0.0001). We evidenced correlation between rest and exercise tests, especially in group 0 (between VO2max and FVC, FEV1, VC, IC; inverse relation between VE/VCO2slope and FVC, FEV1 and VC), but also in group 1 (VO2max and IC), group 2 (VO2max and FVC and FEV1); never in group 3. Discussion: According with literature, we found a frequent impairment of rest pulmonary function in all groups, but especially in group 2 and 3. Restrictive pattern was the most frequent alteration probably due to compromised pulmonary (vascular and alveolar) development secondary to hypoperfusion in fetal and pre-surgery (and pre-TCPC)life. Parenchymal fibrosis, pleural adhesions and thoracic deformities can add further limitation, as showed by the correlation between group 3 and number of surgical intervention. Exercise tests were limited, particularly in group 3 (complex anatomy and lost of chronotropic response), and we found correlations between rest and exercise tests in all but group 3. We speculate that in this patients hemodynamic exceeds respiratory contribution, though markedly decreased.

Studio della funzionalità respiratoria in soggetti con sindrome di Turner

The aim of this study is to evaluate the pulmonary function in subjects with diagnosis of Turner Syndrome, in charge at the Syndromology Ward of the Paediatric Clinic of S.Orsola-Malpighi hospital. There are very few datas about lung function in patients with Turner syndrome’s genotype and phenotype in medical literature. Since the thorax of these subjects have peculiar anatomic shape (as “shield” or “overturned triangle”), we presupposed that these subjects could have also a peculiar respiratory function. Moreover we look for the possibility of correlation between pulmonary function and estroprogestinic replacement therapy and/or growth hormone (GH) replacement therapy. Material and methods: we studied 48 patients, with diagnosis of Turner Syndrome; they all made spirometry voluntarily and, when capable, also plethismografy. Results: - the parametres of pulmonary function are a little higher of the predicted values for age and sex but they are a little lower if they're corrected for each patient’s ideal high and weight: so we can conclude that in Turner Syndrme subjects pulmonary function is normal; -there’s not a statistically significant correlation between pulmonary function and GH therapy; -there’s not a statistically significant correlation between GH therapy’s length and pulmonary function except for Total Lung Capacity which increases with the number of years of GH therapy; - there’s not a statistically significant correlation between pulmonary function and estroprogestinic replacement herapy.

Risultati funzionali a lungo termine dopo sutura o plicatura del diaframma

Obbiettivo. Analizzare la funzionalità polmonare e diaframmatica dopo interventi di plicatura del diaframma con rete di rinforzo peri-costale eseguiti per relaxatio e riparazione di ernia transdiaframmatica cronica mediante riduzione e sutura diretta. Metodi. Dal 1996 al 2010, 10 pazienti con relaxatio unilaterale del diaframma e 6 pazienti con ernia transdiaframmatica cronica misconosciuta sono stati sottoposti a chirurgia elettiva. Gli accertamenti preoperatori e al follow-up di 12 mesi includevano prove di funzionalità respiratoria, misura della pressione massimale inspiratoria alla bocca in clino e ortostatismo, emogasanlisi, TC del torace e dispnea score. Risultati. I pazienti dei due gruppi non differivano in termini di funzionalità respiratoria preoperatoria nè di complicanze postoperatorie; al follow-up a 12 mesi il gruppo Eventrazione mostrava un significativo aumento del FEV1% (+18,2 – p<0.001), FVC% (+12,8 – p<0.001), DLCO% (+6,84 – p=0,04) e pO2 (+9,8 mmHg – p<0.001). Al contrario nrl gruppo Ernia solo il miglioramento della pO2 era significativo (+8.3 – p=0.04). Sebbene la massima pressione inspiratoria (PImax) fosse aumentata in entrambi i gruppi al follow-up, i pazienti operati per ernia mostravano un miglioramento limitato con persistente caduta significativa della PImax dall’ortostatismo al clinostatismo (p<0.001). Il Transitional dyspnoea score è stato concordante con tali miglioramenti pur senza differenze significative tra i due gruppi. La TC del torace ha evidenziato una sopraelevazione dell’emidiaframma suturato, senza recidiva di ernia, mentre i pazienti sottoposti a plicatura hanno mantenuto l’ipercorrezione. Conclusioni. L’utilizzo di un rinforzo protesico è sicuro e sembra assicurare risultati funzionali migliori a distanza in termini di flussi respiratori e di movimento paradosso del diaframma (valutato mediante PImax). Lacerazioni estese del diaframma coinvolgenti le branche principali di suddivisione del nervo frenico si associano verosimilmente a una relaxatio che può quindi ridurre il guadagno funzionale a lungo termine se non adeguatamente trattata mediante l’utilizzo di un rinforzo protesico.

The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease

The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.

Clonal analysis of Inquilinus limosus isolates from six cystic fibrosis patients and specific serum antibody response

Inquilinus limosus is a novel Gram-negative bacterium of the subdivision alpha-Proteobacteria recently found in the airways of patients with cystic fibrosis (CF). Here, the authors report on the clinical courses of six CF patients colonized with I. limosus. Five patients suffered from either an acute respiratory exacerbation or a progressive loss of pulmonary function, whereas one patient was in a stable clinical situation. This study focused on two aims: (i) the clonal analysis of I. limosus isolates by random amplified polymorphic DNA (RAPD)-PCR, and (ii) the clarification of whether the presence of I. limosus in the respiratory tract is associated with a specific serum antibody response. Serum IgG was detected by immunoblotting using I. limosus whole-cell-lysate proteins as antigens. Sera from healthy blood donors (n=10) and from CF patients colonized with Pseudomonas aeruginosa (n=10) were found to be immunoblot negative. All six Inquilinus-positive patients raised serum IgG antibodies against various I. limosus antigens. Surprisingly, in one patient, a specific I. limosus serum antibody response was already detected 1 year prior to Inquilinus-positive sputum cultures. Two prominent antigens were characterized by MALDI-MS: a 23 kDa protein revealed homology to the outer membrane lipoprotein OmlA of Actinobacillus pleuropneumoniae, and an 18 kDa protein to a protein-tyrosine phosphatase of Burkholderia cepacia. In conclusion, detection of I. limosus is accompanied by a specific serum antibody response and may reflect the infectious/pathogenic potential of I. limosus. Moreover, IgG immunoblotting may be useful to detect early infection with I. limosus and may support the selective cultivation of this novel emerging pathogen.

Airway remodelling in children with cystic fibrosis

BACKGROUND: The relationship between airway structural changes and inflammation is unclear in early cystic fibrosis (CF) lung disease. A study was undertaken to determine changes in airway remodelling in children with CF compared with appropriate disease and healthy controls. METHODS: Bronchoalveolar lavage and endobronchial biopsy were performed in a cross-sectional study of 43 children with CF (aged 0.3-16.8 years), 7 children with primary ciliary dyskinesia (PCD), 26 with chronic respiratory symptoms (CRS) investigated for recurrent infection and/or cough and 7 control children with no lower airway symptoms. Inflammatory cells, cytokines, proteases and matrix constituents were measured in bronchoalveolar lavage fluid (BALF). Reticular basement membrane (RBM) thickness was measured on biopsy specimens using light microscopy. RESULTS: Increased concentrations of elastin, glycosaminoglycans and collagen were found in BALF from children with CF compared with the CRS group and controls, each correlating positively with age, neutrophil count and proteases (elastase activity and matrix metalloproteinase-9 (MMP-9) concentration). There were significant negative correlations between certain of these and pulmonary function (forced expiratory volume in 1 s) in the CF group (elastin: r = -0.45, p<0.05; MMP-9:TIMP-1 ratio: r = -0.47, p<0.05). Median RBM thickness was greater in the CF group than in the controls (5.9 microm vs 4.0 microm, p<0.01) and correlated positively with levels of transforming growth factor-beta(1) (TGF-beta(1); r = 0.53, p = 0.01), although not with other inflammatory markers or pulmonary function. CONCLUSIONS: This study provides evidence for two forms of airway remodelling in children with CF: (1) matrix breakdown, related to inflammation, proteolysis and impaired pulmonary function, and (2) RBM thickening, related to TGF-beta(1) concentration but independent of other markers of inflammation.