Progressive Loss Of Pulmonary Function Research Articles

Hippo signaling impairs alveolar epithelial regeneration in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) consists of fibrotic alveolar remodeling and progressive loss of pulmonary function. Genetic and experimental evidence indicate that chronic alveolar injury and failure to properly repair the respiratory epithelium are intrinsic to IPF pathogenesis. Loss of alveolar type 2 (AT2) stem cells or mutations that either impair their self-renewal and/or impair their differentiation into AT1 cells can serve as a trigger of pulmonary fibrosis. Recent reports indicate increased YAP activity in respiratory epithelial cells in IPF lungs. Individual IPF epithelial cells with aberrant YAP activation in bronchiolized regions frequently co-express AT1, AT2, conducting airway selective markers and even mesenchymal or EMT markers, demonstrating 'indeterminate' states of differentiation and suggesting that aberrant YAP signaling might promote pulmonary fibrosis. Yet, Yap and Taz have recently also been shown to be important for AT1 cell maintenance and alveolar epithelial regeneration after Streptococcus pneumoniae induced injury. To investigate how epithelial Yap/Taz might promote pulmonary fibrosis or drive alveolar epithelial regeneration, we inactivated the Hippo pathway in AT2 stem cells resulting in increased nuclear Yap/Taz and found that this promotes their alveolar regenerative capacity and reduces pulmonary fibrosis following bleomycin injury by pushing them along the AT1 cell lineage. Vice versa, inactivation of both Yap1 and Wwtr1 (encoding Taz) or Wwtr1 alone in AT2 cells stem cells impaired alveolar epithelial regeneration and resulted in increased pulmonary fibrosis upon bleomycin injury. Interestingly, inactivation of only Yap1 in AT2 stem cells promoted alveolar epithelial regeneration and reduced pulmonary fibrosis. Together, these data suggest that epithelial Yap promotes, and epithelial Taz reduces pulmonary fibrosis suggesting that targeting Yap but not Taz mediated transcription might help promote AT1 cell regeneration and treat pulmonary fibrosis.

Intracellular replication of Inquilinus limosus in bronchial epithelial cells

Inquilinus limosus is an emerging multi-resistant opportunistic pathogen documented mainly in cystic fibrosis patients. Infection with I. limosus is accompanied by either an acute respiratory exacerbation or a progressive loss of pulmonary function. This study examined the interaction of Inquilinus limosus with the bronquial human epithelial cell line 16HBE14o−. Almost 100% of the bacteria that attached to the bronquial cells were found internalized and located in acidic LAMP2 positive compartments. According to confocal studies combined with antibiotic protection assays, I. limosus is able to survive and eventually replicate in these compartments. I. limosus was found nontoxic to cells and did not induce neither IL-6 nor IL-8 cytokine production, a characteristic that may help the bacteria to evade host immune response. Overall, this study indicates that I. limosus displays pathogenic properties based on its ability to survive intracellularly in epithelial cells eventually leading to antibiotic failure and chronic infection.

Animal models of drug-induced pulmonary fibrosis: an overview of molecular mechanisms and characteristics.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by progressive loss of pulmonary function. Drug-induced interstitial lung disease has been reported as a severe adverse effect of some drugs, such as bleomycin, amiodarone, and methotrexate. Based on good characteristics, drug-induced pulmonary fibrosis (PF) animal model has played a key role in our understanding of the molecular mechanisms of PF pathogenesis and recapitulates the specific pathology in patients and helps develop therapeutic strategies. Here, we summarize the mechanisms and characteristics of given fibrotic drug-induced animal models for PFs. Together with the key publications describing these models, this brief but detailed overview would be helpful for the pharmacological research with animal models of PFs. Potential mechanisms underlying drug induced lung toxicity.

Revealing the Nature of Chronic Obstructive Pulmonary Disease Using Self-tracking and Analysis of Contact Patterns: Longitudinal Study.

BackgroundChronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and is characterized by a progressive loss of pulmonary function over time with intermittent episodes of exacerbations. Rapid and proactive interventions may reduce the burden of the condition for the patients. Telehealth solutions involving self-tracking of vital parameters such as pulmonary function, oxygen saturation, heart rate, and temperature with synchronous communication of health data may become a powerful solution as they enable health care professionals to react with a proactive and adequate response. We have taken this idea to the next level in the Epital Care Model and organized a person-centered technology-assisted ecosystem to provide health services to COPD patients.ObjectiveThe objective is to reveal the nature of COPD by combining technology with a person-centered design aimed to benefit from interactions based on patient-reported outcome data and to assess the needed kind of contacts to best treat exacerbations. We wanted to know the following: (1) What are the incidences of mild, moderate, and severe exacerbations in a mixed population of COPD patients? (2) What are the courses of mild, moderate, and severe exacerbations? And (3) How is the activity and pattern of contacts with health professionals related to the participant conditions?MethodsParticipants were recruited by convenience sampling from November 2013 to December 2015. The participants’ sex, age, forced expiratory volume during the first second, pulse rate, and oxygen saturation were registered at entry. During the study, we registered number of days, number of exacerbations, and number of contact notes coded into care and treatment notes. Each participant was classified according to GOLD I-IV and risk factor group A-D. Participants reported their clinical status using a tablet by answering 4 questions and sending 3 semiautomated measurements.ResultsOf the 87 participants, 11 were in risk factor group A, 24 in B, 13 in C, and 39 in D. The number of observed days was 31,801 days with 12,470 measurements, 1397 care notes, and 1704 treatment notes. A total of 254 exacerbations were treated and only 18 caused hospitalization. Those in risk factor group D had the highest number of hospitalizations (16), exacerbations (151), and contacts (1910). The initial contacts during the first month declined within 3 months to one-third for care contacts and one-half for treatment contacts and reached a plateau after 4 months.ConclusionsThe majority of COPD patients in risk factor group D can be managed virtually, and only 13% of those with severe exacerbations required hospitalization. Contact to the health care professionals decreases markedly within the first months after enrollment. These results provide a new and detailed insight into the course of COPD. We propose a resilience index for virtual clinical management making it easier to compare results across settings.

SAT-141 Glycoprotein NMB (GPNMB) Is Pro-Tumorigenic in TSC2-Null Cancer Cells and Is a Potential Drug Target and Biomarker for Lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women that is characterized by hyperproliferation of smooth muscle cells forming small tumors, or LAM lesions throughout the lungs of patients. Growth of these tumors leads to progressive loss of pulmonary function, and sometimes subsequent lung transplantation. LAM tumor cells contain mutations in either the TSC1 or TSC2 genes, leading to activation of the mTORC1 pathway. In fact, mTOR inhibitors such as sirolimus are commonly used to treat LAM; however, these drugs are not always effective and have significant side effects, suggesting the need for new therapeutic targets. Interestingly, another important feature of LAM cells is that they express melanocytic markers that are normally found in melanocytes or melanoma cells. From RNASeq analysis of a mouse model for LAM that we designed, we discovered significant upregulation of the melanocytic marker Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB), a type I transmembrane protein. GPNMB was not only highly expressed in our mouse model (a uterine specific TSC2-null mouse), it was also expressed in TSC2-null cell lines, and human LAM patient lung samples. In our hands, knocking down GPNMB expression by siRNA directed against GPNMB mRNA decreased migration and proliferation in TSC2-null cells. Additionally, we found that GPNMB’s large ectodomain is shed by TSC2-null cells and can be detected in the blood of human patients with LAM. Finally, MMP 2 and 9 can be secreted as a result of ectodomain shedding and its interaction with integrins. Accordingly, we did indeed see a decrease in MMP 2/9 expression in TSC2-null cells with reduced GPNMB expression from treatment with siRNA directed against GPNMB mRNA. Overall, our results demonstrate the potential importance of GPNMB in LAM tumor progression, and suggest that GPNMB may be a possible LAM biomarker and target for its treatment.

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

Mucociliary clearance is an essential airway defense mechanism dependent predominantly on the proper ciliary function and mucus rheology. The crucial role of cilia is evident in `a variety of respiratory diseases, as the ciliary dysfunction is associated with a progressive decline in lung function over time. The activity of cilia is under supervision of multiple physiological regulators, including second messengers. Their role is to enable a movement in coordinated metachronal waves at certain beat frequency. Ciliary function can be modulated by various stimuli, including agents from the group of beta2 agonists, cholinergic drugs, and adenosine triphosphate (ATP). They trigger cilia to move faster in response to elevated cytoplasmic Ca2+ originated from intracellular sources or replenished from extracellular space. Well-known cilia-stimulatory effect of Ca2+ ions can be abolished or even reversed by modulating the phosphodiesterase (PDE)-mediated breakdown of cyclic adenosine monophosphate (cAMP) since the overall change in ciliary beating has been dependent on the balance between Ca2+ ions and cAMP. Moreover, in chronic respiratory diseases, high ATP levels may contribute to cAMP hydrolysis and thus to a decrease in the ciliary beat frequency (CBF). The role of PDE inhibitors in airway cilia-driven transport may help in prevention of progressive loss of pulmonary function often observed despite current therapy. Furthermore, administration of selective PDE inhibitors by inhalation lowers the risk of their systemic effects. Based on this review we may conclude that selective (PDE1, PDE4) or dual PDE inhibitors (PDE3/4) increase the intracellular level of cyclic nucleotides in airway epithelial cells and thus may be an important target in the development of new inhaled mucokinetic agents. Further research is required to provide evidence of their effectiveness and feasibility regarding their cilia-modulating properties.

Quantitative analysis of airway obstruction in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease with progressive pulmonary function loss caused by progressively proliferating LAM cells. The degree of airway obstruction has not been well investigated within the pathogenesis of LAM.Using a combination of ex vivo computed tomography (CT), microCT and histology, the site and nature of airway obstruction in LAM explant lungs was compared with matched control lungs (n=5 each). The total number of airways per generation, total airway counts, terminal bronchioles number and surface density were compared in LAM versus control.Ex vivo CT analysis demonstrated a reduced number of airways from generation 7 on (p<0.0001) in LAM compared with control, whereas whole-lung microCT analysis confirmed the three- to four-fold reduction in the number of airways. Specimen microCT analysis further demonstrated a four-fold decrease in the number of terminal bronchioles (p=0.0079) and a decreased surface density (p=0.0079). Serial microCT and histology images directly showed the loss of functional airways by collapse of airways on the cysts and filling of the airway by exudate.LAM lungs show a three- to four-fold decrease in the number of (small) airways, caused by cystic destruction which is the likely culprit for the progressive loss of pulmonary function.

The Association Between Vitamin D Status and Pulmonary Function in Pediatric Patients With Cystic Fibrosis

Sufficient vitamin D levels play an essential role in bone health and, more recently, in pulmonary function. Achieving sufficient vitamin D levels is challenging, especially among individuals with malabsorptive diseases, such as cystic fibrosis (CF). Cystic fibrosis is characterized by a progressive loss of pulmonary function and fat malabsorption, increasing the risk for vitamin D deficiency. After reviewing the literature for pediatric patients with CF, the association between vitamin D status and pulmonary function remains unclear. More studies are needed to evaluate whether adequate vitamin D status can assist in maintaining pulmonary function and slowing disease progression.

FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury.

SummaryIdiopathic pulmonary fibrosis is a common form of interstitial lung disease resulting in alveolar remodeling and progressive loss of pulmonary function because of chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts.

Narrative medicine educational project to improve the care of patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of pulmonary function. Often patients do not adhere to inhaled therapies and this leads clinicians to switch treatments in order to improve control of the symptoms. Narrative medicine is a useful approach that helps healthcare professionals to think over the doctor–patient relationship and how patients live with their disease. The aim of this training project was to teach pulmonologists the basics of narrative medicine: to carefully listen to patients and to practice reflective writing in their relationship with them.Training on narrative medicine and parallel charts was provided through a webinar and a weekly newsletter.Across 362 narratives, written by 74 Italian pulmonologists, 92% of patients had activity limitations at their first visit. The main factor influencing the effectiveness and adherence to therapy was a positive doctor–patient relationship; indeed, if such relationship is difficult, only 21% of patients are able to resume all their activities.After learning the narrative approach, clinicians became aware of the need to spend more time listening to patients, to reflect through writing and to understand more deeply the motivations that lead people towards adherence to new therapies.

Nintedanib for the treatment of idiopathic pulmonary fibrosis

ABSTRACTIntroduction: Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by the progressive loss of pulmonary function, ultimately leading to respiratory failure and death. Two novel compounds, nintedanib and pirfenidone, have shown efficacy in reducing the rate of decline of lung function in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has extensively being studied as a potential angiogenesis inhibitor in clinical against various neoplastic disorders. Afterwards, this compound was successfully tested in IPF.Areas covered: Herein, the authors review the working mechanisms of nintedanib, its pharmacological profile, and its efficacy and safety for patients with IPF.Expert opinion: Nintedanib has shown to be safe and effective in patients with IPF, with a favorable long-term safety profile. There is a lack of comparative trials of pirfenidone and nintedanib, and the choice of treatment is left to the physicians’ judgement. Future directions of nintedanib use are represented by the treatment of progressive fibrosing interstitial lung disease other than IPF, IPF with advanced functional impairment, and lung fibrosis secondary to connective tissue diseases. A promising safety profile for the combinational use of nintedanib and pirfenidone in IPF has also recently emerged.

Insights on persistent airway infection by non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease.

Non-typeable Haemophilus influenzae (NTHi) is the most common bacterial cause of infection of the lower airways in adults with chronic obstructive pulmonary disease (COPD). Infection of the COPD airways causes acute exacerbations, resulting in substantial morbidity and mortality. NTHi has evolved multiple mechanisms to establish infection in the hostile environment of the COPD airways, allowing the pathogen to persist in the airways for months to years. Persistent infection of the COPD airways contributes to chronic airway inflammation that increases symptoms and accelerates the progressive loss of pulmonary function, which is a hallmark of the disease. Persistence mechanisms of NTHi include the expression of multiple redundant adhesins that mediate binding to host cellular and extracellular matrix components. NTHi evades host immune recognition and clearance by invading host epithelial cells, forming biofilms, altering gene expression and displaying surface antigenic variation. NTHi also binds host serum factors that confer serum resistance. Here we discuss the burden of COPD and the role of NTHi infections in the course of the disease. We provide an overview of NTHi mechanisms of persistence that allow the pathogen to establish a niche in the hostile COPD airways.

Progressive Decline of Lung Function in Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) is associated with substantial morbidity in rheumatoid arthritis (RA), but very little is known about its long-term progression. This study was undertaken to investigate the progression of pulmonary disease using a large single-center cohort of patients with RA-associated ILD. Records of all patients with RA-associated ILD seen at Mayo Clinic between 1998 and 2014, with at least 4 weeks follow-up and at least 1 pulmonary function test, were identified and manually screened for study inclusion. Progression was defined as a diffusing capacity for carbon monoxide (DLco) <40% predicted (or patients whose illness was too advanced to undergo screening) or a forced vital capacity (FVC) <50% predicted. Time to progression was analyzed using the Kaplan-Meier method. Of the 167 patients included in the study, 81 (49%) were female, with a mean ± SD age of 67 ± 10 years at diagnosis of ILD. Median follow-up time from diagnosis of ILD was 3.3 years (range 0.01-14.8). One-third of the patients required supplemental oxygen, 40% developed DLco <40% predicted, and 22% developed FVC <50% predicted within 5 years after ILD diagnosis. Usual interstitial pneumonia (UIP) versus nonspecific interstitial pneumonia (NSIP) was a risk factor for DLco progression (hazard ratio 3.29 [95% confidence interval 1.28-8.41]). Lower DLco and FVC at baseline increased the risk for progression to DLco <40% predicted and FVC <50% predicted, and higher rates of change in the first 6 months also increased the risk of progression. Progressive loss of pulmonary function is common in RA-associated ILD and is worse in patients with UIP than in those with NSIP. Predictors of progression in patients with RA-associated ILD may aid clinicians in identifying patients at highest risk for progression of ILD.

Idebenone as a Novel Therapeutic Approach for Duchenne Muscular Dystrophy

Progressive loss of pulmonary function leads to early morbidity and mortality in Duchenne muscular dystrophy (DMD) due to both expiratory impairment with ineffective airway clearance, and inspiratory impairment leading to nocturnal and daytime hypoventilation and respiratory failure. Glucocorticoid steroids have become a mainstay of DMD therapy with well-documented efficacy on muscle strength and respiratory function. However, the side-effect profile restricts their long-term use, particularly in non-ambulant patients. Idebenone improves secondary mitochondrial dysfunction caused by dystrophin deficiency, intracellular calcium accumulation and increased reactive oxygen species (ROS). Idebenone-mediated improved bioenergetics leads to enhanced adenosine triphosphate (ATP) production and reduced ROS. Based on this rationale, idebenone has been investigated clinically for efficacy on reducing respiratory function decline in exploratory phase II (DELPHI) and confirmatory phase III (DELOS) trials. Idebenone significantly reduced the loss of respiratory function in 8–18-year-old DMD patients who were not using concomitant glucocorticoids. These results indicate that idebenone can modify the natural course of respiratory disease progression in DMD, which is relevant in clinical practice where loss of respiratory function continues to be a predominant cause of early morbidity and mortality in DMD.

Advances in pediatric asthma in 2009: Gaining control of childhood asthma

This year's summary will focus on recent advances in pediatric asthma as reported in Journal of Allergy and Clinical Immunology publications in 2009. New National Asthma Education and Prevention Program asthma guidelines were released in 2007, with a particular emphasis on asthma control. Now that we have worked with the principals of the guidelines for 2 years, new insights are reported on how to implement the guidelines into clinical practice. This year's report will focus on gaps in management that need to be addressed, including health disparities, methods to improve asthma management through opportunities available in school-based asthma programs, and more information on the development of asthma in childhood. This information brings us closer to the point of managing children with controllable asthma and understanding reasons why asthma is not controlled in the remaining children. If we can close these gaps through better communication, improvements in the health care system, and new insights into treatment, we will move closer to better methods to intervene early in the course of the disease and induce clinical remission as quickly as possible in most children.

A Receptor-targeted Nanocomplex Vector System Optimized for Respiratory Gene Transfer

A Receptor-targeted Nanocomplex Vector System Optimized for Respiratory Gene Transfer

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.

Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study

Reduced lung function is a feature of chronic asthma, which becomes apparent at school age. Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with persistent asthma. We investigated the role of allergic sensitisation and allergen exposure early in life. The German Multicentre Allergy Study followed 1314 children from birth to 13 years of age. We regularly interviewed parents about their child's asthma and measured IgE levels. Allergen exposure was assessed at age 6 months, 18 months, and at 3, 4, and 5 years; lung function was assessed at 7, 10, and 13 years; post-bronchodilator response at 10 and 13 years; and a bronchial histamine challenge was done at 7 years. 90% of children with wheeze but no atopy lost their symptoms at school age and retained normal lung function at puberty. By contrast, sensitisation to perennial allergens (eg, house dust mite, cat and dog hair) developing in the first 3 years of life was associated with a loss of lung function at school age. Concomitant exposure to high levels of perennial allergens early in life aggravated this process: forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was 87.4 (SD 7.4) for those sensitised and with high exposure compared with 92.6 (6.0) for those not sensitised, p<0.0001; and maximal expiratory flow at 50% (MEF50) 86.4 (25.1) for sensitised and with high exposure compared with 101.5 (23.2; p=0.0031) for those not sensitised. Such exposure also enhanced the development of airway hyper-responsiveness in sensitised children with wheeze. Sensitisation and exposure later in life had much weaker effects and sensitisation to seasonal allergens did not play a part. The chronic course of asthma characterised by airway hyper-responsiveness and impairment of lung function at school age is determined by continuing allergic airway inflammation beginning in the first 3 years of life. However, children with a non-atopic wheezing phenotype lose their symptoms over school age and retain normal lung function at puberty.

Doxycycline Treatment for Lymphangioleiomyomatosis with Urinary Monitoring for MMPs

To the Editor: Lymphangioleiomyomatosis, a rare lung disease typically affecting women of reproductive age, is characterized by an abnormal proliferation of smooth-muscle cells and the progressive loss of pulmonary function due to destruction of lung parenchyma.1 Long-term survival is rare; in patients with lymphangioleiomyomatosis, respiratory failure often develops within 10 years after diagnosis. Currently, there is no standard-of-care therapy for this disease, although limited success has been reported with hormone therapy or lung transplantation. The destruction of lung parenchyma has been attributed to an environment conducive to proteolysis resulting from increased expression and activity of matrix metalloproteinases (MMPs). MMP-2, in . . .

Association of body composition and lung function in children with cystic fibrosis

Survival in cystic fibrosis has improved significantly in the last 30 years, with major therapeutic goals of delaying the progressive loss of pulmonary function and maintaining normal growth. Dual-energy X-ray absorptiometry (DEXA) was performed in children with cystic fibrosis (CF) to assess both bone mineral density and body composition. We hypothesised that there would be an association between body composition and pulmonary function in children with CF. Fifty subjects with CF (28 males), mean age 12.7 years, participated in the study. Body composition was determined by DEXA. Body mass index (BMI) was calculated from the ratio of weight/height2 (kg/m2). Lung function was assessed by spirometry. Most patients (78%) had mild lung disease. The mean forced expired volume in 1 sec percent predicted (FEV1% predicted) for the 50 patients was 79.2% (range, 24-117%). There was a strong association between FEV1% predicted and BMI (R=0.59, P=0.0001). Fat-free mass had positive association with pulmonary function tests (R=0.30, P=0.03). Although fat mass showed a positive correlation with pulmonary function, this association did not reach statistical significance. In our group of children with CF and mild lung disease, pulmonary function was more strongly associated with BMI than with fat and fat-free mass.