Spirometry Outcomes Research Articles

Prospective longitudinal association between repeated multiple breath washout measurements and computed tomography scores in children with cystic fibrosis

BackgroundProgression of structural lung disease (SLD) is a major risk factor for morbidity in patients with cystic fibrosis (CF). We studied changes in SLD and correlations with spirometry and nitrogen multiple breath washout (N2MBW) outcomes to explore associations in contemporary evolution between structural and functional abnormalities in CF lung disease. MethodsSpirometry-controlled chest-CTs using PRAGMA-CF for scoring extent of SLD, spirometry, and N2MBW were performed at two-year intervals in school-age children with CF. ResultsFifty-seven children aged 6–18 years were included. No significant progression in mean PRAGMA-CF scores was observed. Half of the children showed improvement in the proportion of bronchiectasis (%Bx). Lung Clearance Index (LCI) and the second moment ratio (M2) increased significantly and baseline values correlated significantly with SLD at follow-up (p ≤ 0.0002). The correlation between the change in M2 (∆M2) and the change in total SLD was R = 0.27 (p = 0.048). We found high negative predictive values (100%) for ∆M2<10% to exclude progression in SLD. For stable or improving values of LCI and M2, the predicted probability for progression in SLD was 16% and 14%, respectively (upper 95% confidence limit: 33%). Evolution in N2MBW and CT outcomes was discordant in half of the children. ConclusionsWe found no progression in SLD over 2 years in school-age children with CF, in contrast to both LCI and M2, which along with discordant outcomes in half of the children underlines that N2MBW and CT assess different aspects of CF lung disease. However, stable outcomes from N2MBW were associated with stable structural lung disease.

Persistent tachypnea of infancy: Follow up at school age.

Persistent tachypnea of infancy (PTI) is a rare pediatric lung disease of unknown origin. The diagnosis can be made by clinical presentation and chest high resolution computed tomography after exclusion of other causes. Clinical courses beyond infancy have rarely been assessed. Patients included in the Kids Lung Register diagnosed with PTI as infants and now older than 5 years were identified. Initial presentation, extrapulmonary comorbidities, spirometry and clinical outcome were analyzed. Thirty-five children older than 5 years with PTI diagnosed as infants were analyzed. At the age of 5 years, 74% of the patients were reported as asymptomatic and did not develope new symptoms during the observational period at school-age (mean, 3.9 years; range, 0.3-6.3). At the age of about 10 years, none of the symptomatic children had abnormal oxygen saturation during sleep or exercise anymore. Lung function tests and breathing frequency were within normal values throughout the entire observational period. PTI is a pulmonary disease that can lead to respiratory insufficiency in infancy. As at school age most of the previously chronically affected children became asymptomatic and did not develop new symptoms. We conclude that the overall clinical course is favorable.

Effect of hypertonic saline on mucociliary clearance and clinical outcomes in chronic bronchitis.

BackgroundMucus dehydration and impaired mucus clearance are common features of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). In CF, inhaled hypertonic saline (HS) improves lung function and produces sustained increases in mucociliary clearance (MCC). We hypothesised that administration of HS (7% NaCl) twice daily for 2 weeks would improve clinical outcomes and produce sustained increases in MCC in COPD subjects with a chronic bronchitis (CB) phenotype.MethodsTwenty-two CB subjects completed a double-blinded, crossover study comparing inhaled HS to a hypotonic control solution (0.12% saline) administered via nebuliser twice daily for 2 weeks. Treatment order was randomised. During each treatment period, symptoms and spirometry were measured. MCC was measured at baseline, shortly after initial study agent administration, and approximately 12 h after the final dose.ResultsHS was safe and well tolerated but overall produced no significant improvements in spirometry or patient-reported outcomes. CB subjects had slower baseline MCC than healthy subjects. The MCC rates over 60 min (Ave60Clr) in CB subjects following 2 weeks of HS were not different from 0.12% saline but were slower than baseline (Ave60Clr was 9.1±6.3% at baseline versus 5.3±6.9% after HS; p<0.05). Subgroup analyses determined that subjects with residual baseline central lung clearance (14 subjects) had improved spirometry and symptoms following treatment with HS, but not 0.12% saline, treatment.ConclusionsInhaled HS appeared to be safe in a general CB population. A specific phenotypic subgroup may benefit from HS but requires additional study.

Changes in Respiratory Function and Physical Capacity among Smokers after Switching to IQOS: One Year Follow-Up

Background: Combustible cigarettes (CC) smoking is a common risk factor for chronic obstructive pulmonary disease (COPD), which is the fourth leading cause of death in Kazakhstan. Switching to "heat-not-burn" tobacco products (IQOS) has been shown to have less deleterious health effect compared to CC for those who cannot quit smoking. The goal of the study was to explore respiratory and physical effects of switching from CC to IQOS in a population of long-time smokers in Kazakhstan. Methods: Two cohorts of men and women aged between 40 and 59 residing in Almaty (a large two-million city of Kazakhstan) were recruited into two cohort of 801 CC smokers and 400 IQOS users and matched by gender, age, education, and smoking history. Analyses also included 627 CC smokers and 308 IQOS users who maintained their tobacco product use during the first year of observation. Spirometry measurements and the 6-minute walk test (6MWT) were performed as a part of the baseline and one-year comprehensive assessments. In addition to spirometry, clinical assessments included components of metabolic syndrome and anthropometry. For comparative analysis between two cohorts Student’s t-test and Chi-squared tests were used. Results: We observed significantly better outcomes for IQOS users in most of CAT scores, spirometry outcomes, and in some metabolic syndrome components. Although changes in the results between the baseline and the one-year assessments show comparable results, smokers of CC often show significantly faster decline in the health status compared to IQOS. Specifically, the changes in CAT score and in spirometry FEV1 over FVC ratios were worsening at higher pace for CC smokers compared to IQOS users. Conclusions: After one year of observation IQOS users demonstrated better outcomes for most of CAT scores and in the ratio of FEV1 over FVC in comparison to CC smokers.

Improved Clinical Outcome After Treatment of Mycobacterium abscessus Complex Pulmonary Disease in Children With Cystic Fibrosis.

Mycobacterium abscessus complex pulmonary disease (M. abscessus PD) in cystic fibrosis (CF) is challenging to treat. Current guideline therapeutic regimens involving an intensive phase of intravenous (IV) antibiotics followed by a consolidation phase of inhaled and oral antibiotics are not evidence-based. The objectives of this study were to characterize the clinical outcomes and clearance of Mycobacterium abscessus complex (M. abscessus) from respiratory cultures in children with CF M. abscessus PD. This retrospective longitudinal cohort analysis evaluated the first course of treatment for M. abscessus PD in 33 children in Queensland, Australia between 2001 and 2015. Spirometry and nutritional outcomes 2 years pretreatment and 1 year posttreatment were compared with clearance or relapse/persistence of Mycobacterium abscessus complex from respiratory cultures. Nine of 18 children who completed therapy, cleared infection. Three of 7 children who completed only intensive therapy cleared sputum compared with 0/8 children who did not. The trajectory of the percent predicted forced expiratory volume in 1 s and age standardized body mass index significantly improved posttreatment in those that cleared sputum (P < 0.0001). These results suggest that current treatment recommendations for M. abscessus PD are associated with some success in clearing infection in children with CF and improvement in lung function and body mass index. Clinical trials are required to determine the best treatment approaches.

GLPG1837, a CFTR potentiator, in p.Gly551Asp (G551D)-CF patients: An open-label, single-arm, phase 2a study (SAPHIRA1)

BackgroundInvestigation of novel cystic fibrosis transmembrane conductance regulator (CFTR) potentiators, such as GLPG1837, for CF patients with gating mutations is challenging as trials require patients to withhold ivacaftor, the current standard of care. This study explored the feasibility of such a study and the impact of one-week ivacaftor withdrawal. MethodsThis open-label, single-arm study aimed to enrol 32 adults ≥18 years of age with CF and at least one p.Gly551Asp (G551D) mutation. Patients received three increasing GLPG1837 dosages twice-daily for two 7-day and one 14-day period following a one-week ivacaftor washout. The primary outcome was safety; secondary outcomes were changes in sweat chloride concentration, spirometry outcomes, and pharmacokinetics. ResultsTwenty-six patients enrolled; 24 completed the study. Adverse events were reported by53.8–76.9% of patients (dosage-dependent), with respiratory adverse events most common. Mean sweat chloride concentrations decreased from 97.7 mmol/L (baseline) to 68.7 mmol/L (end of GLPG1837 treatment). In ivacaftor-pre-treated patients, mean sweat chloride concentrations rose from 42.5 mmol/L at screening to 98.5 mmol/L after ivacaftor washout. Levels were decreased following GLPG1837 treatment (to 68.8 mmol/L at treatment end). Percent predicted forced expiratory volume in 1 s declined from 73.3% at screening to 68.5% after ivacaftor washout but returned to screening level at treatment end (73.1%). ConclusionsPatient willingness to participate in the study suggests that the need for a short period of ivacaftor withdrawal may not be a barrier to development of novel potentiators, such as GLPG1837. A one-week ivacaftor washout was generally well tolerated, but resulted in a decline in lung function, which was reversed with GLPG1837 treatment to pre-washout levels. Combined with the concentration-dependent decrease in sweat chloride concentration, results show that GLPG1837 increases CFTR activity in G551D-CF patients. FundThis work was supported by Galapagos NV. Clinical trial registration numbersNCT02707562; EudraCT 2015-003291-77.

Lung Function Abnormalities in Sickle Cell Anaemia.

Background Abnormalities in lung function tests have been shown to commonly occur in a majority of patients with sickle cell disease (SCD) even at steady state. The prevalence and pattern of these lung function abnormalities have been described in other populations but this is unknown among our sickle cell cohort. There is generally little information available on risk factors associated with the lung function abnormalities and its relevance in patient care. Method This was an analytical cross-sectional study involving 76 clinically stable, hydroxyurea-naive adult Hb-SS participants and 76 nonsickle cell disease (non-SCD) controls. A structured questionnaire was used to obtain sociodemographic data and clinical history of the participants. Investigations performed included spirometry, pulse oximetry, tricuspid regurgitant jet velocity (TRV) measurements via echocardiogram, complete blood counts, free plasma haemoglobin, serum urea, and creatinine. Results Weight, BMI, mean FVC, and FEV1% predicted values were comparatively lower among the Hb-SS patients (p < 0.001). Abnormal spirometry outcome occurred in 70.4% of Hb-SS patients, predominantly restrictive defects (p < 0.001), and showed no significant association with steady-state Hb, WBC count, free plasma haemoglobin, frequency of sickling crisis, chronic leg ulcers, and TRV measurements (p > 0.05). The mean oxygen saturation was comparatively lower among Hb-SS patients (p < 0.001). Conclusion Measured lung volumes were significantly lower in Hb-SS patients when compared to non-SCD controls and this difference was not influenced by anthropometric variance. Lung function abnormalities, particularly restrictive defects, are prevalent in Hb-SS patients but showed no significant association with recognized markers of disease severity.

Abnormal preschool Lung Clearance Index (LCI) reflects clinical status and predicts lower spirometry later in childhood in cystic fibrosis

BackgroundClinical and prognostic value of preschool Multiple Breath Washout (MBW) remains unclear. MethodsInitial MBW results (Exhalyzer® D, EcoMedics AG) in preschool Cystic Fibrosis (CF) subjects (age 2–6 years) at a time of clinical stability were compared to (1) concurrent clinical status measures and (2) later spirometry outcomes. Abnormal Lung Clearance Index (LCI) was defined using published reference data (ULN for LCI 8.0). ResultsLCI was abnormal in 56% (28/50), with mean (SD) LCI 8.61(1.85) at age 4.71(1.3) years. Abnormal LCI was associated with higher dornase alfa use, previous positive bacterial cultures and pF508.del homozygous genotype. Later spirometry (n = 44; mean (SD) 2.3(0.5) years after MBW) demonstrated that abnormal initial preschool LCI was a strong predictor of lower later spirometry outcomes. ConclusionAbnormal preschool LCI was associated with concurrent measures of clinical status and later spirometry deficits, suggesting early prognostic utility of MBW testing in this age range.

Lung Function Impairment in Pediatric Subjects with Sickle Cell Anemia from Nigeria Is Associatede with Associated Low Steady Haemoglobin

Low hemoglobin (Hb) level at steady state in subjects with sickle cell anemia (SCA) may indicate severe chronic hemolysis and might be related to a more severe course of disease.In this study we investigated the hypothesis that low hemoglobin at steady state may be associated with higher rate of lung function impairment in children and adolescents with SCA.MethodsIn this cross-sectional study black African subjects with SCA (Hb phenotype SS) aged 6 to 18 years followed at the Barau Dikko Teaching Hospital, Kaduna, Nigeria, underwent spirometry and anthropometry measures. A recent Hemoglobin level at steady state was recorded for each patient. Caregivers or patients were interviewed through a questionnaire investigating a history of asthma or acute chest syndrome (ACS) and frequency of pain crises in the last year that required analgesics for at least 24 hours. Exclusion criteria were: the lack of recorded complete blood count (CBC) performed in the last 6 months, respiratory symptoms or feeling unwell on the test day, SCA-related acute events (e.g., pain crises) in the last two weeks or a blood transfusion or an ACS episode in the last month. A portable Easy-on-PC spirometer (ndd, Zurich, Switzerland) was used. Data were included if at least two forced expiratory manoeuvres met the ATS/ERS acceptability and repeatability criteria adapted for children (Miller MR, ERJ 2005; Kirkby J, Pediatr.Pulmonol.2008). Spirometry z-scores and percentage of predicted for FEV1, FVC and FEV1/FVC were derived according to the GLI-2012 reference equations for African Americans (Quanjer PH, ERJ2012). Spirometry patterns were classified as normal, obstructive (zFVC ≥ 1.64 + zFEV1/FVC < -1.64), restrictive (zFVC < -1.64 + zFEV1/FVC ≥ -1.64) or mixed (zFVC < -1.64 + zFEV1/FVC < -1.64) and a FEV1 < 70% of predicted was considered indicative of lung end-organ disease (Kassim AA et al, Blood. 2015 Sep 24;126(13):1544-50). Group comparison between patients with Hb level < 7.5 g/dL versus Hb ≥7.5 g/dL were tested using unpaired t test, χ2 or Fisher's exact test as appropriate. The relationship between Hb values and spirometry outcomes was explored through logistic and linear regression models. P-value < 0.05 was adopted as representing a statistically significant difference. Analyses were conducted using the software STATA and Graphpad Prism 7.ResultsA total of 186 subjects with SCA were initially enrolled. Only one child was on hydroxyurea. After exclusions, data from 126 patients (mean ± SD age of 11.5 ± 3.1 yr., 53% boys) were retained for the final analysis. Mean ± SD Hb value was 7.8±0.9 g/dL (range 5.6 to 10.9). Frequency of low Hb (< 7.5 g/dL) at steady state was 30.9% (39/126).Mean FEV1 and FVC z-scores were lower and frequency of FEV1 < 70% of predicted was higher in patients in the low Hb group compared to those with Hb ≥7.5 g/dL though differences were not statistically significant (table 1). Prevalence of restrictive spirometry pattern, possibly suggesting restrictive lung disease, was significant higher in patients with Hb level < 7.5 g/dL (17/39, 43.5%) than in those with Hb ≥7.5 g/dL (20/87, 22.9%) (p = 0.01; table 1).The odds ratio for restrictive spirometry pattern in presence of Hb level <7.5 g/dL was 2.5 (95% CI 1.1 to 5.7; p = 0.03). In a linear regression model (figure 1) the FVC z-score resulted significantly related to the Hb level with an increase of 0.17 z-scores for each point of Hb (95% CI 0.01 to 0.34, p = 0.04; R2 = 0.03).Frequency of asthma, pain crises and previous acute chest syndrome did was similar between the two groups (data not showed)ConclusionsIn Nigerian pediatric patients with sickle cell anemia a hemoglobin level < 7.5 g/dL at steady state was associated with a 2.5 higher risk of presenting a restrictive spirometry pattern and with a higher frequency of end-organ lung disease (FEV1 < 70% of predicted). Low hemoglobin levels in wellbeing may depend on intense chronic haemolysis that could worsen microangiopathy, inflammation and ischemia and reperfusion injury in the lungs, potentially determining a precocious onset of restrictive lung disease.These preliminary data seem to indicate that a low Hb level at steady state in African pediatric patients with sickle cell anemia is associated with more severe lung impairment and should prompt respiratory assessment with lung function when found. [Display omitted] DisclosuresInusa:Novartis plc: Honoraria, Research Funding, Speakers Bureau; Astrazeneca: Consultancy.

Restrictive Spirometry Pattern, Cardiac Structure and Function, and Incident Heart Failure in African Americans. The Jackson Heart Study.

Although chronic obstructive pulmonary disease has been related to heart failure, the relationship between the restrictive spirometry pattern (forced vital capacity [FVC] < 80% predicted with preserved forced expiratory volume in 1 second [FEV1]/FVC ratio) and heart failure is poorly understood. To determine whether having a restrictive spirometry pattern is associated with incident heart failure hospitalization. Community-dwelling African Americans from the Jackson Heart Study (total n = 5,306; analyzed n = 4,210 with spirometry and heart failure outcome data) were grouped by restrictive spirometry (FEV1/FVC ≥ 0.70, FVC < 80%; n = 840), airflow obstruction (FEV1/FVC < 0.70; n = 341), and normal spirometry (FEV1/FVC ≥ 0.70, FVC ≥ 80%; n = 3,029) at the time of baseline examination in 2000-2004. We assessed relationships of echocardiographic parameters and biomarkers with spirometry patterns using regression models. Incident heart failure was defined as an adjudicated hospitalization for heart failure after January 1, 2005 in subjects with no self-reported heart failure history. We used multivariable-adjusted Poisson regression models and Cox proportional hazards models, with death treated as a competing risk in the Cox models, to test associations between spirometry patterns and incident heart failure. We also modeled the association of FVC% predicted with heart failure hospitalization risk using a restricted cubic spline after excluding subjects with airflow obstruction. At the time of baseline spirometry, participants with restrictive spirometry had a median age of 57.2 years (interquartile range, 47.8-64.1); 38.1% were male. Compared with normal spirometry, restrictive spirometry was associated with a higher transmitral early (E) wave velocity to atrial (A) wave velocity ratio, higher pulmonary artery systolic pressure, and higher endothelin levels. After a median follow-up time of 8.0 years, 8.0% of subjects with restrictive spirometry (n = 67) had developed incident heart failure, compared with 3.8% of those with normal spirometry (n = 115) and 10.6% of those with airflow obstruction (n = 36). After risk adjustment, both a restrictive pattern (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.1-2.0) and airflow obstruction (HR, 1.7; 95% CI, 1.1-2.5) were associated with increased rates of incident heart failure hospitalization compared with normal spirometry. Using flexible modeling, the lowest hazards of heart failure hospitalization were observed around FVC 90-100%, with lower FVC% values associated with an increased incidence of heart failure. Both a restrictive pattern on spirometry and airflow obstruction identify African Americans with impaired lung health at risk for heart failure.

The effect of early growth patterns and lung function on the development of childhood asthma: a population based study

BackgroundInfant weight gain is associated with lower lung function and a higher risk of childhood asthma. Detailed individual childhood growth patterns might be better predictors of childhood respiratory morbidity than...

Lung function trajectories throughout childhood in survivors of very preterm birth: a longitudinal cohort study

Data on longitudinal respiratory follow-up after preterm birth in the surfactant era are scarce and of increasing importance, with concerns that preterm survivors are destined for early onset chronic obstructive airway disease. We aimed to comprehensively assess lung function longitudinally from early childhood to mid-childhood in very preterm children (≤32 weeks gestation), and to explore factors negatively impacting on lung function trajectories. Preterm children (with and without bronchopulmonary dysplasia) and healthy term children as controls were studied. All preterm participants were born at 32 weeks' gestation or earlier at King Edward Memorial Hospital, Perth, WA, Australia, between 1997 and 2003. Bronchopulmonary dysplasia was defined as at least 28 days of supplemental oxygen requirement as assessed at 36 weeks' post-menstrual age. Spirometry, oscillatory mechanics, gas exchange, lung volumes, and respiratory symptoms were assessed at three visits, two in early childhood (4-8 years) and one in mid-childhood (9-12 years). CT of the chest was done in preterm children in mid-childhood. Respiratory symptoms were documented via questionnaire at each visit. Data were analysed longitudinally using linear mixed models. 200 very preterm children (126 with bronchopulmonary dysplasia and 74 without bronchopulmonary dysplasia) and 67 healthy term control children attended 458 visits between age 4 and 12 years. Chest CT was done on 133 preterm children at a mean age of 10·9 (SD 0·6) years. Preterm children, with and without bronchopulmonary dysplasia, had declines in spirometry z-scores over time compared with controls: forced expiratory volume in 1 s (FEV1), forced expiratory flow at 25-75% of the pulmonary volume, and FEV1/forced vital capacity all declined by at least 0·1 z-score per year in children with bronchopulmonary dysplasia (all p<0·001). Respiratory mechanics and gas exchange also deteriorated over time in children with bronchopulmonary dysplasia (relative to term controls, respiratory system reactance at 8 Hz decreased by -0·05 z-score per year [95% CI -0·08 to -0·01; p=0·006] and diffusing capacity of the lungs for carbon monoxide decreased by -0·03 z-score per year [95% CI -0·06 to -0·01; p=0·048]). Preterm children with bronchial wall thickening on chest CT (suggestive of inflammation) had bigger decreases in spirometry outcomes through childhood. For example, children with bronchial wall thickening on chest CT had an FEV1 z-score decline of -0·61 (95% CI -1·03 to-0·19; p=0·005) more than those without. Similarly, children exposed to tobacco smoke, those with earlier gestation, or those requiring more neonatal supplemental oxygen declined at a faster rate. Lung function trajectories are impaired in survivors of very preterm birth. Survivors with bronchopulmonary dysplasia, ongoing respiratory symptoms, or CT changes reflecting inflammation have the poorest trajectories and might be at increased risk of lung disease in later life. Close targeted pulmonary follow-up of these individuals is necessary. National Health and Medical Research Council grants APP634519, APP1073301 (to SJS), APP1077691 (to JJP), and APP1025550 (to GLH), Princess Margret Hospital Foundation, and Raine Medical Foundation.

Spirometry in undernourished children in sub-Saharan African

Malnutrition remains a major public health concern in the world today. Estimates from 2015 show that 156 million children under 5 years of age were stunted, and 50 million were wasted (1). Both acute and chronic undernutrition are known to have lasting effects on health (2,3), however the impact of malnutrition on one vital organ: the lungs, is still unclear. This, in part, has to do with the lack of suitable reference for spirometry outcomes for children in areas most affected by undernutrition, such as sub-Saharan Africa.

Validation of Global Lung Function Initiative and All Ages Reference Equations for Forced Spirometry in Healthy Spanish Preschoolers

IntroductionRecent publication of multi-ethnic spirometry reference equations for subjects aged from 3 to 95 years aim to avoid age-related discontinuities and provide a worldwide standard for interpreting spirometric test results. ObjectivesTo assess the agreement of the Global Lung Function Initiative (GLI-2012) and All ages (FEV0.5) reference equations with the Spanish preschool lung function data. To verify the appropriateness of these reference values for clinical use in Spanish preschool children. MethodsSpirometric measurements were obtained from children aged 3–6 years attending 10 randomly selected schools in Barcelona (Spain). Stanojevic's quality control criteria were applied. z-Scores were calculated for the spirometry outcomes based on the GLI equations. If the z-score (mean) of each parameter was close to 0, with a maximum difference of ±0.5 from the mean and a standard deviation of 1, the GLI-2012 equations would be applicable in our population. ResultsOf 543 children recruited, 405 (74.6%) were ‘healthy’, and of these, 380 were Caucasians. Of these 380, 81.6% (169 females, 141 males) performed technically acceptable and reproducible maneuvers to assess FEVt, and 69.5% achieved a clear end-expiratory plateau. z-Scores for FVC, FEV1, FEV1/FVC, FEV0.75, FEV0.75/FVC, FEV0.5, FEF75 and FEF25–75 all fell within ±0.5, except for FEV1/FVC (0.53 z-scores). ConclusionsGLI equations are appropriate for Spanish preschool children. These data provide further evidence to support widespread application of the GLI reference equations.

Validación de las ecuaciones propuestas por la Iniciativa Global de Función Pulmonar (GLI) y las de Todas las Edades para espirometría forzada en preescolares sanos españoles

IntroductionRecent publication of multi-ethnic spirometry reference equations for subjects aged from 3-95 years aim to avoid age-related discontinuities and provide a worldwide standard for interpreting spirometric test results. ObjectivesTo assess the agreement of the Global Lung Function Initiative (GLI-2012) and All ages (FEV0.5) reference equations with the Spanish preschool lung function data. To verify the appropriateness of these reference values for clinical use in Spanish preschool children. MethodsSpirometric measurements were obtained from children aged 3 to 6 years attending 10 randomly selected schools in Barcelona (Spain). Stanojevic's quality control criteria were applied. Z-scores were calculated for the spirometry outcomes based on the GLI equations. If the z-score (mean) of each parameter was close to 0, with a maximum variance of ± 0.5 from the mean and a standard deviation of 1, the GLI-2012 equations would be applicable in our population. ResultsOf 543 children recruited, 405 (74.6%) were ‘healthy’, and of these, 380 were Caucasians. Of these 380, 81.6% (169 females, 141 males) performed technically acceptable and reproducible maneuvers to assess FEVt, and 69.5% achieved a clear end-expiratory plateau. Z-scores for FVC, FEV1, FEV1/FVC, FEV0.75, FEV0.75/FVC, FEV0.5, FEF75 and FEF25-75 all fell within ± 0.5, except for FEV1/FVC (0.53 z-scores). ConclusionsGLI equations are appropriate for Spanish preschool children. These data provide further evidence to support widespread application of the GLI reference equations.

Evaluation of the Global Lung Initiative 2012 Reference Values for Spirometry in African Children.

Despite the high burden of respiratory disease, no spirometry reference values for African children are available. Investigate whether the Global Lung Initiative (GLI-2012) reference values for spirometry are appropriate for children in sub-Saharan Africa and assess the impact of malnutrition on lung function. Anthropometry and spirometry were obtained in children aged 6 to 12 years from urban and semiurban schools in three African countries. Spirometry z-scores were derived using the GLI-2012 prediction equations for African Americans. Thinness (body mass index z-score < -2) was a surrogate for malnutrition. Spirometry outcomes were compared with those of African American children from the third National Health and Nutrition Survey. Spirometry data were analyzed from 1,082 schoolchildren (51% boys) aged 6.0 to 12.8 years in Angola (n = 306), Democratic Republic of the Congo (n = 377), and Madagascar (n = 399). GLI-2012 provided a good fit with mean (SD) z-scores of -0.11 (0.83) for FEV1, -0.08 (0.86) for FVC, and -0.07 (0.83) for FEV1/FVC. Because of low scatter, the fifth centile corresponded to -1.3 z-scores in boys and -1.5 z-scores in girls. Malnourished African children had a normal FEV1/FVC ratio but significant reductions of ∼0.5 z-scores (∼5%) in FEV1 and FVC compared with African American peers from the third National Health and Nutrition Survey. Children in Angola had the lowest, and those in Madagascar had the highest, zFEV1 and zFVC. The results of this study support the use of GLI-2012 reference values for schoolchildren in sub-Saharan Africa. Malnutrition affects body growth, leading to a proportionately smaller FEV1 and FVC without respiratory impairment, as shown by the normal FEV1/FVC ratio.

Assessing bronchodilator response in preschool children using spirometry

BackgroundMeasuring lung function, including bronchodilator response (BDR), is an integral part of asthma management in older children. While spirometry is possible in preschool-aged children, the question remains whether measuring BDR...

Olodaterol for the treatment of chronic obstructive pulmonary disease.

Published data on the pharmacology, pharmacokinetics, efficacy, and safety of the once-daily, long-acting β2-agonist (LABA) olodaterol are reviewed. Olodaterol (Striverdi Respimat, Boehringer Ingelheim), a LABA with high selectivity for β2-adrenergic receptors, is indicated for the treatment of chronic obstructive pulmonary disease (COPD); the recommended dose is 5 μg, to be delivered once daily via the Respimat inhaler. In 48- and 6-week Phase III clinical trials of olodaterol evaluating various lung function and symptomatic outcomes in patients with moderate to very severe COPD, olodaterol use was associated with significant improvements in spirometry outcomes, such as postbronchodilator forced expiratory volume in one second (FEV1), as well as dyspnea severity and quality-of-life measures. Other clinical trials demonstrated that olodaterol produced beneficial effects on FEV1 measures throughout the 24-hour dosing interval. A meta-analysis of data from 20 published research reports indicated that olodaterol's efficacy was comparable to that of the once-daily LABA indacaterol and that the combination of olodaterol and tiotropium provided improvements in lung function greater than those provided by tiotropium alone. Analysis of pooled data from four long-term trials showed that olodaterol's safety profile was comparable to that of formoterol; the most frequently reported adverse effects associated with olodaterol use were bronchitis, nasopharyngitis, and upper respiratory tract infection. Once-daily olodaterol 5 μg is an effective therapy in improving lung function and symptomatic outcomes in patients with moderate to very severe COPD receiving other maintenance therapy, with a satisfactory safety profile.

Telemonitoring in Cystic Fibrosis: A 4-year Assessment and Simulation for the Next 6 Years.

BackgroundInnovative technologies and informatics offer a wide range of services to health districts, doctors, nurses, and patients, and is changing the traditional concept of health care. In the last few years, the availability of portable devices, their easiness to transport and use, and the capability to collect and transmit various clinical data have resulted in the fast development of telemedicine. However, despite its potential impact in improving patient conditions, and its cost effectiveness reported in literature, telemedicine is not in daily practice.ObjectiveThe aim of this study is to provide evidence of the positive impact of telemonitoring proving the sustainability of an application by sending spirometry outcomes from patients’ homes to the hospital doctors via the Internet, and from doctors to patients by an additional phone call solution.MethodsWe examined collected data related to clinical improvement of patients with cystic fibrosis (CF). The patients were followed-up at home using telemonitoring for a period of 10 years, with the aims to prove the sustainability of the methodology (transmissions of spirometry from the patients' home to the doctors and feedback from the doctors to the patients by phone call from the hospital). We stored and analyzed all spirometry transmissions received, and tested the possible presence to decrease the costs between the standard clinical trial (only ambulatory visits) and standard clinical trial with telemonitoring for the follow-up of patients with CF (telemedicine). This was done through an economic analysis of the costs for patients followed at home by telemonitoring. We assessed four years of observation and a simulation of total long-term costs between 2010 and 2020.ResultsWe discovered a potential saving of €40,397.00 per patient for 10 years, actualized at €36,802.97 for the follow-up of all patients enrolled.ConclusionsThe results from the study suggest that telemedicine can improve the health of patients with CF. It is a relatively cheap and potentially sustainable solution, compared to standard clinical trials. However, to establish and prove the long-term effectiveness and cost-effectiveness, more controlled psychological and behavioral studies are needed.

A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis

BackgroundOutcome measures that can evaluate treatment efficacy are important to enhance development of new therapeutic agents for Cystic Fibrosis (CF). We investigated whether the lung clearance index (LCI) measured by multiple breath washout (MBW) can detect a treatment effect of hypertonic saline (HS) inhalation after single dosing within a 24 h period. MethodsIn this randomized controlled cross-over trial, CF patients received inhalation of HS and isotonic saline (IS). MBW and spirometry were performed at 5 time points over 24 h. LCI was measured using both a nitrogen washout technique (LCIN2) and sulfur hexafluoride as a tracer gas (LCISF6). The primary endpoint was the change in the LCIN2 between baseline and 24 h. Secondary endpoints included change in LCISF6 and spirometry outcomes. ResultsTwenty-one patients were randomized. Sixteen completed all study visits and all time point measurements. Eighteen patients contributed to the intention to treat analysis. Significant changes were not detected for either LCI or the spirometry outcomes. However, the primary outcome parameter (change in LCI between the baseline visits and 24 h after inhalation) demonstrated a trend towards improved LCI, in the HS treatment arm compared with the IS treatment arm, −0.60 LCIN2 (SE 0.32), p = 0.08); similar trends were not observed for spirometric measures. The overall effect size of HS was smaller than in previous studies of longer duration. ConclusionsThese data suggest that LCI may potentially be used as an outcome measure in early phase trials with therapeutic agents that have a larger treatment effects than a single inhalation of HS.