Moderate Lung Disease Research Articles

Factors that correlate with sleep oxygenation in children with cystic fibrosis

Cystic fibrosis (CF) patients may develop hypoxemia during sleep. Limited information is available on nocturnal oxygen saturation in CF children with less severe lung disease. The aim of this study was to investigate the degree of nocturnal oxygen desaturation and factors that correlate with nocturnal oxygenation in CF children with normal pulmonary function tests (PFTs) or mild to moderate lung disease. Awake resting and post-exercise SpO2 were measured by pulse oximetry. Each patient had overnight oximetry monitorization at home. Six minutes walk test (6MWT), Shwachman-Kulczycki (S-K), Brasfield and computed tomography (CT) scores, blood gas analysis and nutritional status of patients were evaluated. Twenty-four patients with a median age of 9.5 years were included. Nocturnal mean SpO2 did not differ according to the severity of lung disease based on PFT. However, lowest SpO2 obtained was lower in children with both mild and moderate lung disease compared to normals (87.4% vs. 91.7%, respectively, p = 0.009). 95.8% of CF children with normal PFT or mild to moderate lung disease had desaturation events during sleep. Nocturnal mean SpO2 correlated with S-K (Spearman's rho = 0.64, p < 0.0001), Brasfield (Spearman's rho = 0.31, p = 0.007) and CT scores (Spearman's rho = -0.67, p < 0.0001) as well as PaO2 (Spearman's rho = 0.28, p = 0.021), SaO2 (Spearman's rho = 0.28, p = 0.023), z-score of weight (Spearman's rho = 0.23, p = 0.20) and height (Spearman's rho = 0.20, p = 0.30), there was no correlation with 6MWT. In CF children with normal PFT or mild-to-moderate lung disease, nocturnal oxygenation may correlate with S-K, Brasfield and CT scores as well as PaO2, SaO2, z-score of weight and height.

COMMUNITY-ACQUIRED ACINETOBACTER BAUMANII PNEUMONIA IN A 75-YEAR-OLD VETERAN.

Acinetobacter baumanii is a well-known causative agent of nosocomial infections. However, community-acquired A. baumanii pneumonia is rare in the United States; thus, we present this case of community-acquired pneumonia with a fulminant course. A 75-year-old Caucasian male with hypertension, moderate chronic obstructive lung disease, alcoholism, and diabetes mellitus presented with dyspnea, changes in behavior, hypotension, and hypoxemia with diffuse wheezes and crackles. Chest radiography showed dense right base infiltrate. He had profound respiratory distress started on BiPAP support and was treated with azithromycin and ceftriaxone. Blood Gram stain showed gram-negative diplococci, suggesting Neisseria meningitidis infection. CSF fluid was negative for infection. Final blood culture grew A. baumanii. Antibiotics were changed to imipenem and vancomycin. His condition continued to deteriorate, and the patient9s family decided to withdraw care, leading to the patient9s demise. Risk factors associated with community-acquired Acinetobacter pneumonia are smoking, significant alcohol use, and/or concomitant comorbid conditions (COPD, HTN, DM). Patients present with fever, cough, and dyspnea and progresses to shock with a very fulminant course. A HIGH index of suspicion is warranted during the initial course. The organism has been described as a gram-negative coccibacilli. Rarely, as in our case, it may initially be described as a gram-negative diplococcus, leading to the delay in appropriate therapy. With the increasing prevalence of hospital-acquired Acinetobacter infection, we need to maintain high vigilance in the bacterial flora responsible for community-acquired pneumonia.

Breathing Pattern Adopted by Children with Cystic Fibrosis with Mild to Moderate Pulmonary Impairment during Exercise

Background: It is well known that severe lung impairment in cystic fibrosis (CF) may compromise respiratory muscle function at rest. Even though patients with CF and severe obstructive lung disease exhibit an abnormal breathing pattern during exercise (due to expiratory flow limitation), patients with CF and normal lung function reportedly have a normal breathing pattern. Objectives: The aim of the study was to assess the precise characteristics of the ventilatory pattern adopted during exercise by children with CF and mild to moderate lung disease. Methods: Nine children diagnosed as having mild to moderate CF and 9 healthy children with a similar age distribution participated in this study. Both groups performed a continuous incremental cycling protocol. Breathing and timing components were assessed during exercise. Results: Differences in the breathing pattern between children with CF and controls during exercise are illustrated in Hey plot which described a rapid shallow breathing pattern in children with CF. During exercise, children with CF showed a significantly lower mean inspiratory flow than healthy children (p < 0.001), whereas the mean expiratory flow was higher (p < 0.001). Children with CF also showed a significant increase in the end-tidal carbon dioxide pressure, which may indicate the emergence of hypercapnia. Conclusions: During exercise, children with CF (even those not suffering from advanced disease) showed signs of rapid, shallow breathing and an increase in the ventilatory response. This was essentially due to an increase in the mean inspiratory flow, which in turn suggests an expiratory flow limitation. The children were also predisposed to hypercapnia.

Combined Lung-Liver Transplantation in Patients With Cystic Fibrosis

We agree with Dr. Kotru and colleagues regarding the need for additional studies to better identify the specific indications for combined lung-liver transplantation. This is a difficult task, however, mainly limited by the fact the need for this operation is exceedingly rare. There is simply not enough information available on the efficacy of combined lung-liver transplantation to ethically randomize the treatment of cystic fibrosis patients with lung and liver failure. Non-randomized study designs such as risk-based allocation may represent a more feasible means of proceeding. Alternatively, further analysis of a large single-center experience such as the series from Washington University may help identify factors that predict respiratory morbidity and mortality in isolated lung recipients or hepatobiliary morbidity and mortality in isolated lung recipients. Although isolated liver transplantation may improve lung function in patients with mild to moderate cystic fibrosis-related lung disease, we do not feel it is appropriate for patients with severe respiratory disease. Long waiting times are indeed a problem for combined lung-liver transplant candidates, as they are for many other forms of multi-organ transplantation such as liver-intestine transplantation (1). Unfortunately, there is no formal mechanism to minimize these waiting times; requests for exception points may be the best (and only) option currently available. Cystic fibrosis has previously been associated with bile inspissation and obstruction of the intrahepatic bile ducts. Extrahepatic strictures are less common appear in most cases to be caused by inflammation of the head of the pancreas (2). We agree that transplant surgeons should heed caution in performing a duct-to-duct anastomosis in transplant recipients with cystic fibrosis. We have performed four transplants using duct-to-duct anastomosis in cystic fibrosis patients at our institution, however, and have observed no postoperative strictures. Finally, experimental studies have suggested that transplanting a liver or spleen along with a kidney, heart or lung would lead to a decreased incidence of rejection (3–5). In spite of this, there have been no published reports to suggest that this phenomenon is seen in clinical transplantation. Indeed, the frequency with which acute rejection has been reported in combined heart-liver transplantation, for example, suggests that a liver graft does not induce tolerance to a clinically significant degree (6–10). Nonetheless, the decreased incidence of acute pulmonary rejection and bronchiolitis obliterans is notable and deserves further attention.

Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients?

Despite absence of clear proof of efficacy, the use of inhaled corticosteroids (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease. In a prospective double-blind case-controlled study, fluticasone propionate 500 microg or placebo were administered twice daily during 12 months. The mean (standard error of the mean, SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1)) was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups. However, longitudinal growth in fluticasone patients was significantly slower than in placebo patients: 3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over the 12-month study duration. This resulted in a significant change in height standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus -0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1-2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment.

Attitudes Toward Physical Activity in Adolescents With Cystic Fibrosis: Sex Differences After Training: A Pilot Study

This study compared the attitudes of 16 adolescents (8 males and 8 females) with cystic fibrosis (CF) toward exercise and physical activity (PA) before and after a 6-week exercise program. Although the boys and girls had similar ages (12-18 years), the boys were fitter and leaner and had higher pulmonary function. Subjects reported both positive exercise attitudes of self and perceived attitudes of parents/friends that remained essentially unchanged after strenuous training. Boys reported higher vigorous activities at baseline than girls, but all subjects increased participation in very hard PAs after training. Girls had small but nonsignificant increases in PA at each (mild-vigorous) level. Results emphasize that adolescents with a mild to moderate lung disease can significantly increase PA in a nursing intervention.

Alpha-1-antitrypsin replacement therapy: current status

Alpha-1-antitrypsin deficiency is a relatively common genetic disease that predisposes to the development of early-onset emphysema and, in some instances, liver disease. The use of alpha-1-antitrypsin replacement therapy in the treatment of alpha-1-antitrypsin deficiency related emphysema is much debated and the purpose of this review is to examine the results of recent studies. We will comment briefly on the pathogenesis and epidemiology of the disease together with new therapeutic approaches currently under intense research. Several nonrandomized observational studies and one meta-analysis on the clinical effectiveness of alpha-1-antitrypsin replacement treatment showed a favourable result towards reducing forced expiratory volume in 1 s (FEV1) deterioration in alpha-1-antitrypsin-deficient individuals with moderate lung disease or accelerated FEV1 decline. Improved ways of monitoring disease progression, including computed tomography scanning and exacerbations, are being proposed as primary endpoints. Apart from one small randomized, placebo-controlled trial using computed tomography scanning, which showed a trend toward preservation of lung density on scanning with treatment, the literature lacks proof of effectiveness from large randomized trials. There might be a possible, but so far unproven, role of alpha-1-antitrypsin augmentation therapy in reducing the progression of emphysema in subsets of patients with alpha-1-antitrypsin deficiency. Placebo-controlled, randomized clinical trials are required to draw firm conclusions. Recent advances in the understanding of the molecular pathology provide opportunities for development of new therapeutic targets for this genetic disorder.

Reference values for the 6-min walk test in healthy subjects 20–50 years old

In 102 healthy Caucasians, 20-50 years old, we investigated the effect of anthropometrics on the 6-min walk test (6MWT), in order to provide reference values for walk distance (6MWD), oxygen saturation (SpO2), pulse rate (PR), respiratory rate (RR), breathlessness perception (VAS) and for the walking distance and body weight product (DW). The mean 6MWD and DW values were 593 +/- 57 and 638+/-44 m (P < 0.01) and 35,030 +/- 5306 and 48,882 +/- 6555 kg m (P < 0.01), respectively for women and for men. While walking, SpO2 remained unaltered and subjects reached 67 +/- 10% of their maximal predicted heart rate and a RR mean value of 19 +/- 4 bpm. VAS ratings were significantly higher in females as compared to males (24 +/- 15 vs. 18 +/- 5 mm, P < 0.05), however, when corrected for PR change while walking, they were not different. The equation by stepwise multiple regression analysis included height, age and gender for the 6MWD and accounted for 42% of the total variance. This study confirms the relevant effect of anthropometrics on walking capacity and suggests that when rating dyspnea, the change in heart rate during walking should be considered.

High resolution computerized tomography of the chest and pulmonary function testing in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis patients

To evaluate the sensitivity of high-resolution computerized tomography (HRCT) of the chest compared to spirometry measures in evaluating the effects of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF) patients.Thirty-two subjects >/=6 years old with mild to moderate CF lung disease were enrolled in a randomized, double-blind, placebo-controlled pilot study. Duration was 28 days; 31 subjects completed the study.HRCT scores decreased 4.06 +/- 3.20 (mean +/- SD) for TSI and decreased 0.17 +/- 1.78 for placebo subjects (P = 0.13). Mean forced expiratory flow during middle half of forced vital capacity (FEF(25%-75%)) predicted increased 6.08 +/- 4.86 for TSI and decreased 0.60 +/- 2.34 for placebo (P = 0.23). Percentage forced expiratory volume in 1 s (FEV(1)) predicted increased slightly for both TSI and placebo (1.29 +/- 3.33 for TSI and 1.17 +/- 1.4 for placebo) (P = 0.97). Two of eight HRCT component scores (atelectasis and inhomogeneity) were observed to be highly discordant with observed HRCT global total score and other HRCT component scores. A modified total score was calculated by dropping them from the global total score. The modified HRCT total scores decreased 6.68 +/- 3.09 for TSI subjects and increased 0.02 +/- 2.0 for the placebo subjects (P = 0.07). Sample sizes were calculated to show statistical significance by differences in modified total HRCT scores, global total HRCT scores, FEF(25%-75%) predicted or FEV(1) % predicted. A total of 60, 100, 200, and over 800 patients would be necessary respectively.HRCT can be a useful measure of change in CF pulmonary disease, requiring a smaller sample size than that required to show treatment effect by pulmonary function testing (PFT) alone.

47 Denufosol tetrasodium inhalation solution: results from two phase 2 trials in CF patients with mild to moderate lung disease

47 Denufosol tetrasodium inhalation solution: results from two phase 2 trials in CF patients with mild to moderate lung disease

Lung Function Tests in Neonates and Infants with Chronic Lung Disease: Global and Regional Ventilation Inhomogeneity

This review considers measurement of global and regional ventilation inhomogeneity (VI) in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). We focus primarily on multiple-breath inert gas washout (MBW) and electrical impedance tomography (EIT). The literature is critically reviewed and the relevant methods, equipment, and studies are summarized, including the limitations and strengths of individual techniques, together with the availability and appropriateness of any reference data. There has been a recent resurgence of interest in using MBW to monitor lung function within individuals and between different groups. In the mechanically ventilated, sedated, and paralyzed patient, VI indices can identify serial changes occurring following exogenous surfactant. Similarly, global VI indices appear to be increased in infants with CLDI and to differentiate between infants without lung disease and those with mild, moderate, and severe lung disease following preterm birth. While EIT is a relatively new technique, recent studies suggest that it is feasible in newborn infants, and can quantitatively identify changes in regional lung ventilation following alterations to ventilator settings, positive end expiratory pressure (PEEP), and administration of treatments such as surfactant. As such, EIT represents one of the more exciting prospects for continuous bedside pulmonary monitoring. For both techniques, there is an urgent need to establish guidelines regarding data collection, analysis, and interpretation in infants both with and without CLDI.

A Crossover, Randomized, Controlled Trial of Dornase Alfa Before Versus After Physiotherapy in Cystic Fibrosis

Although dornase alfa is a widely used, aerosolized, mucolytic agent in patients with cystic fibrosis (CF), its efficacy in relation to the timing of physiotherapy has not been tested. We sought to determine whether dornase alfa is more efficacious when it is administered 30 minutes before versus 30 minutes after physiotherapy/positive expiratory pressure (PEP) therapy in clinically stable children. Using a crossover, randomized, double-blind, and placebo-controlled trial, we undertook a 6-week study of the efficacy of dornase alfa in relation to the timing of physiotherapy at home. There were 2 treatment orders. Dornase alfa before + placebo after physiotherapy/PEP for 2 weeks was followed by a 2-week washout and then the reverse order placebo before and dornase alfa after physiotherapy/PEP for the final 2 weeks. The second treatment order reversed the placebo and dornase alfa therapy for the first and last 2-week blocks. The main outcome measures used included the change in predicted percentage of forced expiratory volume in 1 second (FEV1), a composite quality of well-being score (QWB), and a measure of aerobic fitness (maximal oxygen consumption, [VO2max]), determined using shuttle testing. Fifty-two patients who had CF (27 female) with mild to moderate suppurative lung disease, were a mean +/- SD age of 10.7 +/- 3.2 years, had Shwachman scores of 86 +/- 11.8, had predicted FEV1 of 83% +/- 18%, had quality of well-being score of 0.76 +/- 0.08, and had VO2max of 42.6 +/- 6.3 ml/kg per min were enrolled. Fifty patients completed the study. Intention-to-treat analysis was used. Nonsignificant mean (95% confidence interval) differences in FEV1 (0.02 L [-0.05 to 0.10]), VO2max (-0.75 ml/kg per min [-1.85 to 0.35]), and QWB (0.005 [-0.94 to 0.0028]) for dornase alfa after physiotherapy/PEP were detected. A post hoc analysis showed that patients who were colonized persistently with Pseudomonas aeruginosa had a significantly greater improvement in FEV1 (0.12 L [0.23 to 0.01] vs -0.04 L [0.05 to -0.13]) when dornase alfa was administered after physiotherapy/PEP. Dornase alfa is equally efficacious when delivered before or after physiotherapy/PEP in patients with CF. Patients who are colonized persistently with P aeruginosa may derive more improvement in FEV1 when dornase alfa is delivered after physiotherapy/PEP.

Computed Tomography in the Evaluation of Cystic Fibrosis Lung Disease

The first report of computed tomography (CT) scanning to monitor cystic fibrosis (CF)-related lung disease was published in 1986. Further publications followed, but in general there was little interest in this technique until recently. Two factors in particular have led to this increased interest. First is an increasing realization that pulmonary function tests, long the mainstay of CF evaluation, often underestimate the presence and severity of mild and moderate lung disease. Second is the need for more sensitive outcome measures to assess new therapies. This had led to new interest and a series of important publications. The goal of this article is to present the current status of CT scanning in CF.

Does carbon dioxide retention during exercise predict a more rapid decline in FEV1 in cystic fibrosis?

Background: Carbon dioxide (CO2) retention during exercise is uncommon in mild to moderate lung disease in cystic fibrosis (CF). The ability to deal with increased CO2 is dependent on the...

1077. Phase I Clinical Trial of Recombinant Adeno-Associated Virus (rAAV)-Alpha-1 Antitrypsin Vectors

Introduction: Several groups have demonstrated that recombinant adeno-associated virus (rAAV) vectors are capable of sustained expression of therapeutic proteins when administered to skeletal muscle. In the case of alpha-1-antitrypsin (AAT) deficiency, a single injection of a rAAV2 vector in mice resulted in sustained AAT secretion at levels that would be therapeutic for prevention of lung disease in humans suffering from this disorder (11|[mu]|M, approximately 800 mg/ml or 80 mg/dl). There is currently no definitive therapy for these patients, since the licensed protein replacement products are in short supply and require weekly intravenous infusions. Recently, we completed the ongoing preclinical testing (mouse, rabbit, and primate) of the rAAV2-AAT vector in muscle, completed clinical grade production of rAAV2-AAT, and initiated a phase I clinical trial of rAAV-AAT gene therapy in patients with AAT deficiency. MEHODS: The trial is an open-labeled, single administration study being performed in a total of 12 adult AAT-deficient patients with mild to moderate lung disease. Four cohorts of three subjects each are being used with a dose escalation between cohorts. The dosages for the four cohorts range from 2.1 |[times]| 1012 vector genomes (vg) per patient to 6.9 |[times]| 1013 vg/patient. Subjects are screened and allowed a 28-day period for washout of their protein replacement. An ultrasound-guided injection technique is used to avoid inadvertent intravascular injection. The primary endpoints of the study assess safety with examinations of the injection site, hematology, chemistry, coagulation studies, and pulmonary function tests. Biological activity of the vector is primarily assessed by detection in the serum of normal M-variant AAT protein by an isoelectric focusing gel/ immunoblot technique. Serum is also assayed for antibodies to rAAV2 capsid and to AAT. Blood and semen DNA are also being assayed for vector DNA sequences.

High-resolution computed tomography in young patients with cystic fibrosis: Distribution of abnormalities and correlation with pulmonary function tests

ObjectiveTo assess pulmonary abnormalities detected by high-resolution computed tomography (HRCT) in young children with cystic fibrosis (CF) and mild to moderate lung disease. Study designHigh-resolution computed tomography was performed in 60 children, 6 to 10 years old, with mild to moderate lung disease (forced expiratory volume in 1 minute [FEV1], 52–137; mean, 102; SD, 15% predicted). HRCTs were scored by using a system that evaluates each lobe for severity and extent of CF lung disease. Findings of CF lung disease were tabulated in all subjects and in a subgroup with normal pulmonary function tests. HRCT scores were correlated with FEV1, forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of expired vital capacity (FEF25-75) in 57 patients. ResultsBronchiectasis was present in 35% of subjects, mucous plugging in 15%, and air trapping in 63%. No abnormality was detected in 25%. In 37 subjects with FEV1, FVC, and FEF25-75 >85% predicted, bronchiectasis was present in 30%. In 17% of these subjects, bronchiectasis was seen in ≥4 lobes. Correlations between HRCT scores and FEV1 were significant and showed fair to moderate correlation (r=0.36–0.46). ConclusionsHigh-resolution computed tomography demonstrated a broad range of pulmonary abnormalities in young patients with CF with mild to moderate lung disease. In this study, abnormalities, including bronchiectasis, were common in young children with CF and normal pulmonary function tests.

Lung Microvascular Adaptation in Infants with Chronic Lung Disease

Microvascular development is critical for normal lung maturation. The aims of this study were (1) to quantitatively and qualitatively assess lung microvascular growth in the human fetus, from 22 to 40 weeks’ gestation, and (2) to compare development in these infants to those with mild, moderate and severe chronic lung disease (CLD). Using 1- and 4-µm thick sections and electron microscopy, lungs were morphometrically assessed for surface density of distal air spaces; volume density of parenchymal vessels having an air-blood barrier (ABB); percent of distal air space wall having an ABB, and capillary loading, defined as ABB/mm² of epithelial surface area. The percent of vessels with ABB increased in controls during development in parallel with increasing lung parenchyma. Infants with severe CLD had fewer ABBs and less capillary loading than controls up to 34 weeks’ post-conceptional age (PCA), but by 36–40 weeks, showed catch-up growth. Microvasculature vessel diameter, septal thickness, and air sac diameter at 36–40 weeks’ PCA were increased with severe CLD, and vessels were more distant from the air surface. We conclude that infants with severe CLD have both stunted secondary septation and microvascular development, but over time, the primary septal wall adapts by thinning and increasing the number of ABBs, thereby taking on the function of secondary septa.

Effects of creatine supplementation in cystic fibrosis: results of a pilot study

Background: The CF transmembrane conductance regulator (CFTR), whose mutations cause cystic fibrosis (CF), depends on ATP for activation and transport function. Availability of ATP in the cell and even more in specific cellular microcompartments often depends on a functional creatine kinase system, which provides the ‘energy buffer’ phosphocreatine. Creatine supplementation has been shown to increase phosphocreatine levels, thus promoting muscle growth and strength in athletes and having protective effects in neuromuscular disorders. Aim: To test clinically, if creatine supplementation improves maximal isometric muscle strength (MIMS), lung function and CFTR channel activity in patients with CF, and to determine enzymatic activity of creatine kinase in respiratory epithelial cells. Methods: In an open-label pilot study 18 CF patients (8–18-year-old) with pancreatic insufficiency and mild to moderate lung disease received daily creatine supplementation during 12 weeks. Patients were monitored during 24–36 weeks. Enzymatic activity of creatine kinase was measured in primary epithelial cell cultures. Results: After creatine supplementation, there was no change in lung function and sweat electrolyte concentrations, possibly due to the very low creatine kinase activities detected in respiratory epithelia. However, the patients consistently showed signicantly increased MIMS (18.4%; P<0.0001), as well as improved general well-being, as assessed by a standardized questionnaire. Except for one patient with transient muscle pain, no side effects were reported. Conclusions: Our pilot study suggests, that creatine supplementation should be further evaluated as a possible clinically beneficial adjuvant therapy for patients with CF to increase muscle strength, body-weight and well-being

Low lung function and incident lung cancer in the United States: data From the First National Health and Nutrition Examination Survey follow-up.

Obstructive lung disease and lung cancer are tobacco-related diseases that can remain clinically silent until late in the disease process. We sought to define the risk for incident lung cancer among a national cohort of US adults with and without obstructive lung disease. We studied participants in the First National Health and Nutrition Examination Survey, who had up to 22 years of follow-up. We classified subjects as having moderate or severe obstructive lung disease at baseline if the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) was less than 70% and the FEV1 was less than 80% of the predicted value. We also determined incident cases of lung cancer during the follow-up period. A total of 113 lung cancers occurred in the 5402 adults in the cohort. In the proportional hazards model adjusted for covariates of age, sex, race, education, smoking status, and duration and intensity of smoking, the presence of moderate or severe obstructive lung disease was associated with a higher risk for incident lung cancer (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4). The presence of moderate or severe obstructive lung disease is a significant predictor of incident lung cancer in long-term follow-up. This finding may be useful clinically and in studies evaluating the utility of new tools for the early detection of lung cancer.

Six-Minute Walking Test in Cystic Fibrosis Adults With Mild to Moderate Lung Disease: Comparison to Healthy Subjects.

Six-Minute Walking Test in Cystic Fibrosis Adults With Mild to Moderate Lung Disease: Comparison to Healthy Subjects.