Small Airway Obstruction Research Articles

Does the Duration of Ofloxacin Otic Drops Matter in Immediate Post‐tube Otorrhea?

Objective: The effect of upper respiratory tract diseases on phonation has been reviewed, but the effect of lower respiratory tract diseases on phonation has been little studied. The influence of asthma as a reversible obstructive small airway disease on phonatory variables is not clear yet. Method: This cross sectional, case control trial was performed from March to September 2008 to evaluate the quality of phonation in asthma. Eight vocal parameters were evaluated in 34 asthmatic patients and a control group by a voice meter device using Dr Speech statistical software. Results: Vocal variables such as FO, Jitter, and Shimmer were almost similar in both groups statistically. This fact likely reflects the normal phonatory mechanism at the level of vocal cords in asthmatic patients, but harshness, hoarseness, NNE, S/Z ratio ( P < .01) and breathy voice ( P = .015) were different statistically. This indicates the role of the lower airway in the phonation process. Conclusion: Small airway diseases such as asthma may have direct effect on phonation, but we suggest further studies with more cases.

Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation

Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n = 24) or large airway deposition (n = 25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF(75%)). FEF(75%) increased significantly by 0.7 sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the small airways group. Intention-to-treat analysis did not show a significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p = 0.06) in FEF(75%) Z-score and a significant difference (p = 0.04) between groups in absolute FEF(75%) (L · s(-1)) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF(75%) in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.

Comparison of alveolar nitric oxide concentrations using two different methods for assessing small airways obstruction in asthma

Fractional exhaled nitric oxide (F(E) NO) is considered a potentially useful biomarker for airway inflammation. A two-compartment model (2CM) of pulmonary NO dynamics has been used for the evaluation of bronchial NO flux (J'awNO) and alveolar NO concentration (C(A) NO) in asthmatic patients. Recently, the trumpet shape of the airway tree and axial diffusion (TMAD) model has been reported as a modification of the 2CM. This study was designed to determine the validity of C(A) NO measurement using the TMAD model for assessing small airways inflammation in asthma. A total of 52 asthmatic patients and 12 normal control subjects were included in the study. Methacholine inhalation challenge and pulmonary function tests, sputum induction, and exhaled NO measurements at several flow rates were performed. J'awNO and C(A) NO were calculated using both the 2CM (C(A) NO( 2CM) , J'awNO( 2CM) ) and TMAD models (C(A) NO( TMAD) , J'awNO( TMAD) ). Both J'awNO (J'awNO( 2CM) and J'awNO( TMAD) ) and C(A) NO (C(A) NO( 2CM) and C(A) NO( TMAD) ) were significantly higher in asthmatic patients than in control subjects. C(A) NO( 2CM) was significantly correlated with FEV(1) /FVC (r = -0.35, P = 0.01), FEF(25-75) (r = -0.45, P < 0.001) and sputum eosinophils (r = 0.32, P = 0.02). In contrast, C(A) NO( TMAD) was significantly correlated with FEF(25-75) (r = -0.42, P = 0.002) but not with FEV(1) /FVC or sputum eosinophils. C(A) NO( TMAD) is more specific as an indicator of small airways obstruction than C(A) NO( 2CM) . Assessment of small airways obstruction using the TMAD model may clarify the role of the small airways in the pathogenesis of asthma.

Reduced apoptosis of CD8+ T-Lymphocytes in the airways of smokers with mild/moderate COPD

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation in airways and lung parenchyma. CD8+ T-lymphocytes, crucial effector and regulatory cells in inflammation, are increased in the central and peripheral airways in COPD. The aim of this study was to assess the role of apoptosis in the accumulation of CD8+ T-lymphocytes within the airway wall in COPD. We examined the submucosa of transverse sections of central and peripheral airways from post-operative tissues from non-smokers (n=16), smokers with normal lung function (n=16), smokers with mild/moderate COPD (n=16), and smokers with severe/very severe COPD (n=9). TUNEL and immunohistochemistry techniques were used to identify apoptosis and cell phenotype, respectively. The percentage of apoptotic CD8+ T-lymphocytes was significantly lower (p<0.0001) in smokers with mild/moderate COPD than in non-smokers, smokers with normal lung function, and smokers with severe/very severe COPD, and was positively related to values of FEV(1) and FEV(1)/FVC ratio, both in central and in peripheral airways. These data suggest that reduced apoptosis of CD8+ T-lymphocytes may be an important mechanism that contributes to the accumulation of these cells in the airway submucosa in smokers with mild/moderate COPD.

Neuroendocrine Cell Distribution and Frequency Distinguish Neuroendocrine Cell Hyperplasia of Infancy From Other Pulmonary Disorders

The diagnostic gold standard for neuroendocrine cell hyperplasia of infancy (NEHI) is demonstration of increased numbers of neuroendocrine cells (NECs) amid otherwise near-normal lung histology. Typical clinical and radiographic features often are present. However, NECs are also increased after lung injury and in other disorders, which can complicate biopsy specimen interpretation and diagnosis of suspected NEHI. Our objective was to determine whether NEC prominence is specific for the diagnosis of NEHI. Bombesin immunoreactivity was quantified in lung biopsy specimens from 13 children with characteristic clinical presentation and imaging appearance of NEHI. The primary comparison group was 13 age-matched patients selected from children with lung disorders that are known to be associated with NEC prominence. Bombesin-immunopositive epithelial area was significantly increased in NEHI compared with other diseases. Patchy bronchiolar inflammation or fibrosis was frequently observed in NEHI, with no direct association between airway histopathology and bombesin-immunopositive area. NEC prominence correlated with severity of small airway obstruction demonstrated on infant pulmonary function testing. Immunohistochemical colocalization of bombesin with Ki67 did not reveal active NEC proliferation. There was wide intra- and intersubject variability in NEC number, which did not relate to radiographic appearance of the region biopsied. Our findings demonstrate that NEC prominence is a distinguishing feature of NEHI independent of airway injury. The extent of intrasubject variability and potential for overlap with control subjects suggest that clinical-radiologic-pathologic correlation is required for diagnosis and that the abundance of NECs may not fully explain the disease pathogenesis.

Influence of bronchial blood flow and conductance on pulmonary function in stable systolic heart failure

The aim of this study was to determine the relationship between airway blood flow (Q(aw)), airway conductance (G(f-aw)) and pulmonary function in patients with stable HF. 12 controls (CTRL: age=63±9 years, FVC=98±15%pred, LVEF=61±6%) (all data presented as mean±SD), 16 patients with mild HF (HF-A, NYHA I-II: age=64±9 years, FVC=90±17%pred, LVEF=28±6%), and 14 patients with moderate/severe HF (HF-B, NYHA III-IV: age=65±6 years, FVC=84±12%pred, LVEF=26±6%) were studied. Q(aw) was assessed using soluble gas measurements; perfusion pressure across airway bed (ΔP(aw)) was estimated from systemic and pulmonary pressure measurements; G(f-aw) was calculated as Q(aw)/ΔP(aw); PF was assessed by spirometry. While Q˙(aw) was not significantly different between CTRL (61.3±17.9 μL min(-1)mL(-1)), HF-A (70.1±26.9 μL min(-1)mL(-1)) and HF-B (56.2±14.9 μL min(-1)mL(-1)) groups, G(f-aw), was elevated in HF-A (1.1±0.4 μL min(-1)mL(-1)mm Hg(-1), p<0.03) and tended to be elevated in HF-B (1.2±0.6 μL min(-1)mL(-1)mm Hg(-1), p=0.07) when compared to CTRL (0.8±0.3 μL min(-1)mL(-1)mm Hg(-1)). Significant positive correlations were found between G(f-aw) and RV/TLC for HF-A (r=0.63, p<0.02) and HF-B (r=0.58, p<0.05). These results support the hypothesis that increased bronchial conductance and bronchial congestion may be related to greater small airway obstruction and as such may play a role in the PF abnormalities and symptoms of congestion commonly observed in HF patients.

Opportunities and Challenges in the Genetics of COPD 2010: An International COPD Genetics Conference Report

Opportunities and Challenges in the Genetics of COPD 2010: An International COPD Genetics Conference Report

Small airway obstruction in patients with rheumatoid arthritis

This work was intended to evaluate the prevalence of obstructive small-airway disease in patients with rheumatoid arthritis (RA) and its association with clinical characteristics. Pulmonary function testing (PFT) and high-resolution computed tomography (HRCT) were performed on 189 consecutive RA patients. Each case was diagnosed based on abnormal HRCT findings. We defined obstructive dysfunction of small airways as a forced expiratory flow from 25% to 75% of vital capacity (FEF25–75) value >1.96 residual standard deviation (RSD) below predicted values. We found 19 patients (10.1%) with an interstitial pneumonia (IP) pattern and 15 (7.9%) with a bronchiolitis pattern; the other 155 (82.0%) had no abnormal HRCT patterns. In patients with neither abnormal pattern, median values of percentage predicted for carbon monoxide diffusing capacity (DLCO) and ratio of DLCO to alveolar ventilation (DLco/VA) were within the normal range, but median FEF25–75, forced expiratory flow at 25% of vital capacity (V25), and V25/height were <70% of predicted values. Forty-seven patients (30.3%) in this group had obstructive small-airway dysfunction. Multivariate logistic regression analysis indicated that this type of abnormality is strongly associated with respiratory symptoms [odds ratio (OR) 5.18; 95% confidence interval (CI) 1.70–15.75; p = 0.012), smoking history (OR 2.78; 95% CI 1.10–6.99; p = 0.03), and disease duration >10 years (OR 2.86; 95% CI 1.27–6.48; p = 0.012). Parenchymal micronodules, bronchial-wall thickening, and bronchial dilatation on HRCT scans were also predictive factors for abnormal FEF25–75, although these morphological changes were too limited for us to diagnose these patients with the bronchiolitis pattern. Obstructive dysfunction of small airways is apparently common among RA patients, even among those with neither the IP nor the bronchiolitis pattern on HRCT scans. Factors significantly associated with abnormal FEF25–75 are respiratory symptoms, smoking history, and RA duration.

Vascular endothelial growth factor in bronchoalveolar lavage fluid in sulfur mustard exposed lung patients.

To determine the levels of vascular endothelial growth factor isoform consisting of 165 amino acids (VEGF165) in Bronchoalveolar Lavage Fluid from Mustard Exposed Patients. Bronchoscopy with Bronchoalveolar Lavage was performed on sulphur mustard exposed patients. A total of 39 patients with documented exposure to Sulfur Mustard during the Iran-Iraq war participated in this study, of which 38 patients were males and one patient was female. The mean±SD age of patients was 41 ± 6.6 years. The mean time after exposure to sulfur mustard was 19 ±1.7 years. Eighteen patients had concomitant war injuries but they were not related to the respiratory system. While Twenty-two patients had a history of submassive persistent hemoptysis. There was no case with massive hemoptysis. Most of the patients had small airway obstruction (FEV1/FVC% = 78.14 ± 9.76 and FEV1% =82.79±18.23). Twenty-three patients had significant air trapping in the chest. High Resolution Computed Tomography was compatible with BOS. VEGF165 concentrations in BALF were 36.87 ± 34.68 pg/ml. When corrected to total protein of Bronchoalveolar Lavage Fluid (BALF) it was 0.76 ± 0.70 pg/mg. BALF of VEGF did not correlate with hemoptysis or air trapping in chest HRCT. Thus, there was also no correlation between level of VEGF165 in BALF and any of PFT indexes (FVC, FEV1, MMEF or PEF). Although VEGF is one of the cytokines which has an important role in chronic pulmonary disorders, it seems that it has no essential role in the severity of Mustard Lung Disease.

Radiologische Diagnostik bei COPD

Die COPD ist eine heterogene Erkrankung, die durch eine obstruktive Ventilationsstörung definiert ist. Diese Ventilationsstörung entsteht durch eine Kombination individuell unterschiedlich ausgeprägter pathologischer Veränderungen des Lungenparenchyms (Emphysem) und der Atemwege (vor allem Obstruktion kleiner Atemwege). Die Projektionsradiografie kann lediglich ein fortgeschrittenes Emphysem diagnostizieren, ein geringer ausgeprägtes Emphysem und die Atemwegsveränderungen lassen sich vor allem mit der Computertomografie (CT) diagnostizieren.

Respiratory outcomes and atopy in school-age children who were preterm at birth, with and without bronchopulmonary dysplasia

OBJECTIVE:To assess pulmonary function and the prevalence of atopy in school-age children who were very low birth weight as infants and to compare those who had bronchopulmonary dysplasia to those who did not.METHOD:We studied 85 (39 male and 46 female) at a mean age of 84 (range, 62 to 107) months who were very low birth weight infants. Bronchopulmonary dysplasia was defined as oxygen dependency at 36 weeks gestational age. We excluded 8 patients (4 for cerebral palsy and 4 for no collaboration). Detailed perinatal and clinical data were collected. Lung function was evaluated using conventional spirometry. Atopy (assessed by the allergy skin-prick test) was considered when at least one positive skin test occurred in a panel of the most common environmental allergens in the local region. Comparisons between the bronchopulmonary dysplasia and no bronchopulmonary dysplasia groups were performed using the Mann-Whitney, χ2 and Fisher's exact tests.RESULTS:We compared the bronchopulmonary dysplasia (n = 13) and no bronchopulmonary dysplasia (n = 64) groups. Atopy was observed in 4 (30.8%) of the bronchopulmonary dysplasia patients and in 17 (26.6%) of the no bronchopulmonary dysplasia patients (p = 0.742). Two (15.4%) patients with bronchopulmonary dysplasia had a family history of atopy vs. 17 (26.6%) in the no bronchopulmonary dysplasia group (p = 0.5). Lung function tests showed airway obstruction in 2 (15.4%) of the bronchopulmonary dysplasia patients and in 10 (15.6%) of the no bronchopulmonary dysplasia patients (p = 1.0). Four (33.3%) of the bronchopulmonary dysplasia patients had small airway obstruction vs. 14 (22.2%) of the no bronchopulmonary dysplasia patients (p = 0.466).CONCLUSION:Our data showed no significant differences in lung function between bronchopulmonary dysplasia and no bronchopulmonary dysplasia patients at school age and no evidence of an association between atopy and bronchopulmonary dysplasia.

Prevalence of smoking and chronic obstructive pulmonary disease amongst teachers working in Kocaeli, Turkey

AimTo evaluate smoking and COPD prevalence amongst teachers working in the schools of Kocaeli City, Turkey.MethodIn this cross-sectional study, a questionnaire focusing on respiratory symptoms and smoking habits was administered to all participants who accepted to join the study.All subjects also underwent a physical examination and a pulmonary function test performed with portable spirometer. According to GOLD criteria, subjects who had post-bronchodilator FEV1/FVC < 70% and negative reversibility test were classified as COPD.ResultsA total of 685 teachers were included [female n = 307 (45%), male n = 378 (55%)] with mean age 38.9 ± 8.9 years. Smoking habit was evaluated in 660 subjects: 291 (44.1%) were smokers, 252 (38.2%) were non-smokers and 117 (17.7%) were ex-smokers. Pulmonary function test was available in 651 subjects and 510 (78.3%) were defined as normal on spirometric analysis. Small airway obstruction was found in 115 of the cases (17.7%) in whom FEF25-75 level was found to be lower than 70% predicted. FEV1/FVC level was lower than 70% in 16 subjects (2.5%). Five subjects who had positive reversibility test were excluded from the study. The remaining 11 subjects who were considered as COPD consisted of 2 (18%) females and 9 (82%) males. Six of these subjects were aged over 40 years.ConclusionSpirometry has an important role in early diagnosis of COPD. Spirometric evaluation of cases with risk factors for COPD could be helpful in diagnosing patients before the progressive decline in lung function begins. Further studies are needed to evaluate whether the interventional strategies at this stage such as smoking cessation could prevent the progression of disease.

Pulmonary manifestations of Sjögren's syndrome

Sjögren's syndrome is a chronic inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary glands. However, extraglandular organ systems may frequently be involved, including the lungs. Although subclinical pulmonary inflammation exists in more than 50% of patients, clinically significant pulmonary involvement affects approximately 10% of patients and may be the first manifestation of the disease. The entire respiratory tract may be involved, with a wide spectrum of manifestations including xerotrachea and bronchial sicca, obstructive small airway disease, various patterns of interstitial lung disease, lymphoinfiltrative or lymphoproliferative lung disease, such as lymphoma (usually of MALT type), pulmonary hypertension, pleural involvement, lung cysts, and pulmonary amyloidosis.

Small airway obstruction in patients with rheumatoid arthritis.

This work was intended to evaluate the prevalence of obstructive small-airway disease in patients with rheumatoid arthritis (RA) and its association with clinical characteristics. Pulmonary function testing (PFT) and high-resolution computed tomography (HRCT) were performed on 189 consecutive RA patients. Each case was diagnosed based on abnormal HRCT findings. We defined obstructive dysfunction of small airways as a forced expiratory flow from 25% to 75% of vital capacity (FEF25–75) value >1.96 residual standard deviation (RSD) below predicted values. We found 19 patients (10.1%) with an interstitial pneumonia (IP) pattern and 15 (7.9%) with a bronchiolitis pattern; the other 155 (82.0%) had no abnormal HRCT patterns. In patients with neither abnormal pattern, median values of percentage predicted for carbon monoxide diffusing capacity (DLCO) and ratio of DLCO to alveolar ventilation (DLco/VA) were within the normal range, but median FEF25–75, forced expiratory flow at 25% of vital capacity (V25), and V25/height were <70% of predicted values. Forty-seven patients (30.3%) in this group had obstructive small-airway dysfunction. Multivariate logistic regression analysis indicated that this type of abnormality is strongly associated with respiratory symptoms [odds ratio (OR) 5.18; 95% confidence interval (CI) 1.70–15.75; p = 0.012), smoking history (OR 2.78; 95% CI 1.10–6.99; p = 0.03), and disease duration >10 years (OR 2.86; 95% CI 1.27–6.48; p = 0.012). Parenchymal micronodules, bronchial-wall thickening, and bronchial dilatation on HRCT scans were also predictive factors for abnormal FEF25–75, although these morphological changes were too limited for us to diagnose these patients with the bronchiolitis pattern. Obstructive dysfunction of small airways is apparently common among RA patients, even among those with neither the IP nor the bronchiolitis pattern on HRCT scans. Factors significantly associated with abnormal FEF25–75 are respiratory symptoms, smoking history, and RA duration.

Retroperitoneal Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]) is a rare disease of unknown etiology, which almost exclusively affects women of child-bearing age. The disease is characterized histologically by diffuse hamartomatous proliferation of atypical smooth muscle cells in the lung, lymphatic trunk, and lymph nodes and causes gradual obstruction of small airways, lymphatic vessels, and vasculature. 1 The primary target of LAM is the chest, and most previous reports of LAM have concentrated on the pulmonary findings. However, extrapulmonary LAM rarely occurs with or without subsequent involvement of the lung, and several cases of extra-pulmonary LAM involving abdominal or pelvic retroperitoneal organs have been reported in the radiology literature. 2-7 We describe a case of histologically proven retroperitoneal LAM in a female patient with sonography, computed tomography (CT), gadolinium-enhanced magnetic resonance imaging (MRI), and positron emission tomography (PET).

Part 14: Pediatric Advanced Life Support

In contrast to adults, cardiac arrest in infants and children does not usually result from a primary cardiac cause. More often it is the terminal result of progressive respiratory failure or shock, also called an asphyxial arrest. Asphyxia begins with a variable period of systemic hypoxemia, hypercapnea, and acidosis, progresses to bradycardia and hypotension, and culminates with cardiac arrest.1 Another mechanism of cardiac arrest, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), is the initial cardiac rhythm in approximately 5% to 15% of pediatric in-hospital and out-of-hospital cardiac arrests;2,–,9 it is reported in up to 27% of pediatric in-hospital arrests at some point during the resuscitation.6 The incidence of VF/pulseless VT cardiac arrest rises with age.2,4 Increasing evidence suggests that sudden unexpected death in young people can be associated with genetic abnormalities in myocyte ion channels resulting in abnormalities in ion flow (see “Sudden Unexplained Deaths,” below). Since 2010 marks the 50th anniversary of the introduction of cardiopulmonary resuscitation (CPR),10 it seems appropriate to review the progressive improvement in outcome of pediatric resuscitation from cardiac arrest. Survival from in-hospital cardiac arrest in infants and children in the 1980s was around 9%.11,12 Approximately 20 years later, that figure had increased to 17%,13,14 and by 2006, to 27%.15,–,17 In contrast to those favorable results from in-hospital cardiac arrest, overall survival to discharge from out-of-hospital cardiac arrest in infants and children has not changed substantially in 20 years and remains at about 6% (3% for infants and 9% for children and adolescents).7,9 It is unclear why the improvement in outcome from in-hospital cardiac arrest has occurred, although earlier recognition and management of at-risk patients on general inpatient units …

Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010

The term ‘pneumothorax’ was first coined by Itard and then Laennec in 1803 and 1819 respectively,1 and refers to air in the pleural cavity (ie, interspersed between the lung and...

Validity of Measurement of Two Specific Biomarkers for the Assessment of Small Airways Inflammation in Asthma

Background: Small airways inflammation in asthma has been supposed to contribute to instability of the disease and therapy resistance. This study was designed to determine the validity of measurement of Nε-(carboxymethyl)lysine (CML) levels in induced sputum and alveolar concentrations of nitric oxide (NO) for the assessment of small airways inflammation in asthma. Methods: The authors measured CML levels in induced sputum and the bronchial flux (Jno) and alveolar concentration (Calv) of NO in 37 asthmatic patients and 15 normal controls. After initial analysis, all asthmatics were randomly assigned to receive inhaled fluticasone propionate (FP; 400 μg/day, n = 21) or hydrofluoroalkane–beclomethasone dipropionate (HFA-BDP; 400 μg/day, n = 16) for 12 weeks. And then the determination of exhaled NO level and sputum induction was performed after the treatment period. Results. CML levels in induced sputum were significantly higher in asthmatics than in normal controls (median [interquartile range], asthmatics: 53.0 [44.8–64.3] μg/ml, normal controls: 22.0 [14.8–28.3] μg/ml; p < .01). Similarly, Jno and Calv were also higher in asthmatics. Moreover, CML level was closely correlated with Calv but not with Jno in asthmatics (r = .47, p = .005). Jno was significantly correlated with forced expiratory volume in one second/forced vital capacity (FEV1/FVC), and CML level and Calv were correlated with forced expiratory flow between 25% and 75% of FVC (FEF25–75), an index of small airways obstruction. After FP treatment, the decrease in CML level and Calv were very small. In contrast, these levels were markedly decreased after HFA-BDP treatment. Moreover, even after FP or HFA-BDP treatment, CML level was significantly correlated with Calv. Conclusions: This novel, noninvasive technique of measurement of CML levels in induced sputum and Calv may prove to be important not only in the evaluation of small airways inflammation but also in helping us move toward a better understanding of the roles of the small airways in the pathogenesis of asthma.

Abnormalities of plethysmographic lung volumes in asthmatic children

While lung hyperinflation is frequent in asthma, measurement of lung volumes is not recommended in current guidelines. The aim of this descriptive functional study was to assess whether systematic measurement of volumes by plethysmography may detect isolated hyperinflation with normal expiratory flows. One hundred sixty asthmatic children (mean age + or - SD: 10.8 + or - 2.7 years; 50 girls) receiving inhaled corticosteroid underwent lung function tests before and after bronchodilation (BD). To avoid the problem of dysanaptic lung growth on predicted values in childhood, airflow limitation and hyperinflation were defined by ratios (FEV(1,%pred)/FVC(%pred) for the former, RV/TLC for the latter) and values below and above the 5th or 95th percentiles of reference values, were chosen as cut-off values. Different functional phenotypes were evidenced, mainly normal lung function (142/160 [89%] after BD), but also isolated airflow limitation (35/160 [22%] before and 7/160 [4%] after BD) and isolated hyperinflation (17/160 [11%] before and 11/160 [7%] after BD), while the combination of both impairments before BD (13/160 [8%]) was never observed after BD. There was no statistical relationship between airflow limitation and hyperinflation, either before or after BD. Indices of spirometry (FEV(1), FEF(50%)) were unable to predict isolated hyperinflation that corresponds to small airway obstructive syndrome. Isolated hyperinflation is not infrequent in asthmatic children (7-11%) and small airway obstruction is not detected by forced expiratory flows.

Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosis

Fraction of exhaled nitric oxide (FENO) is often reduced in cystic fibrosis (CF). FENO at different expiratory flows can provide an indication of the site of nitric oxide production. The aim of this study was to examine whether NO parameters are related to overall (FEV(1)) or peripheral (lung clearance index, LCI, measured by multiple breath SF(6) washout) airway function and systemic inflammation in CF. Secondary aim was to compare alveolar NO and bronchial NO flux calculated by two different mathematical models, a linear and a nonlinear method. Thirty-five healthy and 45 CF children were recruited. FENO at 50 ml/sec (FENO(50)) and bronchial NO flux were lower in CF than controls, 9.5 (2.7-38.8) (median (range)) versus 12.4 (5.2-40.1) ppb, P = 0.029, and 391 (97-1772) versus 578 (123-1993) (pl/sec), P = 0.036, respectively. No difference in alveolar NO was shown. The nonlinear method resulted in lower alveolar NO and higher bronchial flux, than the linear method, but the result was closely correlated in both groups. LCI was higher in CF than controls, 8.4 (6.5-12.9) versus 5.9 (5.1-7.8), P < 0.001. FENO(50) was negatively correlated with LCI (r = -0.43; P = 0.003) and positively correlated with FEV(1) (r = 0.42, P = 0.004) in CF. Alveolar NO correlated negatively with inflammatory markers: orosomucoid (r = -0.42, P = 0.005), platelets (r = -0.50, P < 0.001) and white blood cell count (r = -0.48, P = 0.001). In conclusion, FENO(50) and bronchial NO flux are reduced in young CF subjects and low FENO(50) is associated with overall and small airway obstruction. NO parameters derived from the different models were closely related but the values differed slightly.