Initial Forced Expiratory Volume Research Articles

A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

Integrating latent classes in the Bayesian shared parameter joint model of longitudinal and survival outcomes.

Cystic fibrosis is a chronic lung disease requiring frequent lung-function monitoring to track acute respiratory events (pulmonary exacerbations). The association between lung-function trajectory and time-to-first exacerbation can be characterized using joint longitudinal-survival modeling. Joint models specified through the shared parameter framework quantify the strength of association between such outcomes but do not incorporate latent sub-populations reflective of heterogeneous disease progression. Conversely, latent class joint models explicitly postulate the existence of sub-populations but do not directly quantify the strength of association. Furthermore, choosing the optimal number of classes using established metrics like deviance information criterion is computationally intensive in complex models. To overcome these limitations, we integrate latent classes in the shared parameter joint model through a fully Bayesian approach. To choose the optimal number of classes, we construct a mixture model assuming more latent classes than present in the data, thereby asymptotically “emptying” superfluous latent classes, provided the Dirichlet prior on class proportions is sufficiently uninformative. Model properties are evaluated in simulation studies. Application to data from the US Cystic Fibrosis Registry supports the existence of three sub-populations corresponding to lung-function trajectories with high initial forced expiratory volume in 1 s (FEV1), rapid FEV1 decline, and low but steady FEV1 progression. The association between FEV1 and hazard of exacerbation was negative in each class, but magnitude varied.

Randomized Clinical Trial Comparing Breath-Enhanced to Conventional Nebulizers in the Treatment of Children with Acute Asthma

To compare the efficacy of a breath-enhanced and a conventional jet nebulizer in the treatment of children with moderate to severe acute asthma. We enrolled subjects between 6 and 18 years of age presenting to the emergency department (ED) with acute asthma and an initial forced expiratory volume in 1 second (FEV1) <70% of predicted. We excluded patients with chronic disease, who required immediate resuscitation, or failed spirometry. Subjects were randomized to breath-enhanced or conventional jet delivery of a 5-mg albuterol treatment. Our primary outcome was change in FEV1, and secondary outcomes included change in clinical asthma scores, ED length of stay, disposition, and side effects. Student t test and multivariable linear regression were used to evaluate the primary outcome. In total, 497 patients were assessed for eligibility with 118 enrolled and 107 subjects available for analysis of the primary outcome. Improvement in FEV1 was significantly greater with conventional jet nebulizer (mean ΔFEV1 +13.8% vs +9.1%, P = .04). This difference remained significant after adjustment for baseline differences. Subgroup analysis of 57 subjects with spirometry meeting American Thoracic Society/European Respiratory Society guidelines yielded similar results (mean ΔFEV1 +14.5% vs +8.5%, P=.03). There were no significant differences in clinical asthma scores, ED length of stay, disposition, or side effects. Albuterol delivered via conventional jet nebulizer resulted in significantly greater improvement in FEV1 than albuterol delivered by breath-enhanced nebulizer, without significant differences in clinical measures. Conventional jet nebulizers may deliver albuterol to children with acute asthma more effectively than breath-enhanced nebulizers. ClinicalTrials.gov: NCT02566902.

Evaluation of alpha-1-antitrypsin levels in blood serum of patients with chronic obstructive pulmonary disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is a disease that causes obstructed air flow from the lungs. The disease also has a dramatic role in increasing rate of mortality and morbidity in recent years. Air pollution, long-term exposure to particulate matter and irritating gases, especially cigarette smoke, genetic inheritance which has an impact on the initial forced expiratory volume one in second (FEV1), and alpha-1-antitrypsin (AAT) deficiency are among common COPD risk factors. The objective of this study is to evaluate parameters and serum AAT levels in COPD patients. Materials and Methods: Having taken the approval of local ethical committee, this cross-sectional study was performed with adult patients diagnosed with COPD, whose serum AAT levels were measured through nephelometric analysis in Kars Harakani State Hospital where secondary health care is served. The study evaluated ATT levels in patients’ serum in relation to their age, gender, body mass (BMI), exposure to cigarette smoke, FEV1 percentage, hospitalization in pulmonology or intensive care unit through a year, mortality status, white blood cell (WBC), c-reactive protein (CRP) and blood gases. Results: Theaverage age of the243 patients included in the study was 68.41±11.52 and 160 (65.8%) of them were male. The age and BMI of the female patients were higher. Of the all patients only a single patient’s serum AAT level was below the reference value. AAT levels were similar in both genders irrespective of their being exposed to cigarette smoke or being discharged or being exitus at their first admission to hospital, being exitus in the first year of disease diagnose, and being hospitalized in intensive care unit. AAT levels were reasonably correlated with WBC and CRP in a positive way (p<0.001 r=0.289 for WBC; p<0.001, r=0.295 for CRP). AAT levels were seen to significantly increase along with COPD stages which go up with FEV1 percentages (p<0.001). CRP was watched to have increased to Stage III COPD (severe COPD). However, it was watched to have decreased in Stage IV (very severe COPD) (p =0.179). Conclusion: In the study, AAT serum levels of COPD patients were examined. The levels and their relations in various parameters of the patients were evaluated. (www.actabiomedica.it)

Prognostic Significance of Large Airway Dimensions on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

Large airway dimensions on computed tomography (CT) have been associated with lung function, symptoms, and exacerbations in chronic obstructive pulmonary disease (COPD), as well as with symptoms in smokers with preserved spirometry. Their prognostic significance in persons without lung disease remains undefined. To examine associations between large airway dimensions on CT and respiratory outcomes in a population-based cohort of adults without prevalent lung disease. The Multi-Ethnic Study of Atherosclerosis recruited participants ages 45-84 years without cardiovascular disease in 2000-2002; we excluded participants with prevalent chronic lower respiratory disease (CLRD). Spirometry was measured in 2004-2006 and 2010-2012. CLRD hospitalizations and deaths were classified by validated criteria through 2014. The average wall thickness for a hypothetical airway of 10-mm lumen perimeter on CT (Pi10) was calculated using measures of airway wall thickness and lumen diameter. Models were adjusted for age, sex, principal components of ancestry, body mass index, smoking, pack-years, scanner, percent emphysema, genetic risk score, and initial forced expiratory volume in 1 second (FEV1) percent predicted. Greater Pi10 was associated with 9% faster FEV1 decline (95% confidence interval [CI], 2 to 15%; P = 0.012) and increased incident COPD (odds ratio, 2.22; 95% CI, 1.43-3.45; P = 0.0004) per standard deviation among 1,830 participants. Over 78,147 person-years, higher Pi10 was associated with a 57% higher risk of first CLRD hospitalization or mortality (P = 0.0496) per standard deviation. Of Pi10's component measures, both greater airway wall thickness and narrower lumen predicted incident COPD and CLRD clinical events. In adults without CLRD, large airway dimensions on CT were prospectively associated with accelerated lung function decline and increased risks of COPD and CLRD hospitalization and mortality.

Mortality Risk and Pulmonary Function in Adults With Cystic Fibrosis at Time of Wait Listing for Lung Transplantation

Lung transplantation (LTx) benefit for survival in cystic fibrosis (CF) patients placed on the wait list is not well studied. To predict the relationship between initial forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and the hazard ratio (HR) associated with LTx in CF patients, the United Network for Organ Sharing database was queried from 2005 to 2006 for adult patients with CF. Survival was assessed from wait list entry time until death on wait list, death after LTx, or censoring. Multivariate Cox proportional hazards models were used to assess the effect of LTx. The first model estimated the HR of LTx with adjustment for FEV1 or FVC and other covariates, and the second model estimated the HR of LTx conditional on FEV1 or FVC at listing. Two hundred seventy-eight patients with CF were included in the cohort, and 277 were used for survival analysis. Lung transplantation reduced the risk for death controlling for FEV1 (HR, 0.601; 95% confidence interval, 0.375 to 0.964; p= 0.035) or controlling for FVC (HR, 0.547; 95% confidence interval,0.336 to 0.889; p= 0.015). Interaction models found that the HR of LTx varied significantly across initialFEV1 and FVC, with the predicted LTx HR and 95% confidence interval being protective (HR < 1) at FEV1 of 25% or less and FVC of 40% or less, respectively. The benefit of LTx in adults with CF was significant at a lower baseline FEV1 than expected. A threshold for baseline FVC was established below which LTx was protective.

Predictors and Outcome of Low Initial Forced Expiratory Volume in 1 Second Measurement in Children with Cystic Fibrosis

To identify the characteristics of children with cystic fibrosis with low initial forced expiratory volume in 1 second (FEV1) % predicted and to investigate their outcome. Patients were categorized into low or high initial FEV1 groups using cluster analysis. Comparisons of the demographic and clinical data were performed between the 2 groups. From 122 children, 21 clustered into the low and 101 into the high FEV1 group. The mean FEV1 was 69% ± 12% predicted for the low and 95% ± 12% predicted for the high FEV1 group (P < .001). The low FEV1 group had lower body mass index percentiles (P = .003), were hospitalized more frequently (P = .001), and had been on dornase alfa longer (P = .006). Low FEV1 group had more patients with positive cultures for Pseudomonas aeruginosa (P = .002) and Stenotrophomonas maltophilia (P < .001) and had more total number of cultures positive for mucoid P. aeruginosa (P = .009) and methicillin resistant Staphylococcus aureus + P. aeruginosa (P = .005). The low FEV1 group continued to have low FEV1 measurements, their FEV1 declined slower, required more hospitalizations per year (P = .01), and had more cultures for mucoid (P = .003) and nonmucoid P. aeruginosa (P = .02) ± methicillin resistant S. aureus (P = .002) in comparison with the high FEV1 group. Poor adherence was associated with lower initial FEV1 values in females, and early, rapid decline of FEV1 in males. Some children with cystic fibrosis may present with poor lung function early in life and continue to have subnormal lung function associated with reduced body mass index, more frequent hospitalization, and higher rates of infection. Such children may benefit from careful evaluation and close follow-up.

Hypereosinophilic obliterative bronchiolitis: a distinct, unrecognised syndrome

Biopsy-proven cases of eosinophilic bronchiolitis have only been reported in isolation, and all come from Japan. We present six patients with hypereosinophilic obliterative bronchiolitis (HOB), defined by the following criteria: 1) blood eosinophil cell count >1 G·L(-1) and/or bronchoalveolar lavage eosinophil count >25%; 2) persistent airflow obstruction despite high-dose inhaled bronchodilators and corticosteroids; and 3) eosinophilic bronchiolitis at lung biopsy (n=1) and/or direct signs of bronchiolitis (centrilobular nodules and branching opacities) on computed tomography (n=6). Chronic dyspnoea and cough which was often severe, without the characteristic features of asthma, were the main clinical manifestations. Atopy and asthma were present in the history of three and two patients, respectively. One patient met biological criteria of the lymphoid variant of idiopathic hypereosinophilic syndrome. Mean blood eosinophil cell count was 2.7 G·L(-1) and mean eosinophil differential percentage at bronchoalveolar lavage was 63%. Mean initial forced expiratory volume in 1 s/forced vital capacity ratio was 50%, normalising with oral corticosteroid therapy in all patients. HOB manifestations recurred when oral prednisone was decreased to 10-20 mg·day(-1), but higher doses controlled the disease. HOB is a characteristic entity deserving to be individualised among the eosinophilic respiratory disorders. Thorough analysis is needed to determine whether unrecognised and/or smouldering HOB may further be a cause of irreversible airflow obstruction in chronic eosinophilic respiratory diseases.

Efficacy of Racemic Albuterol versus Levalbuterol Used as a Continuous Nebulization for the Treatment of Acute Asthma Exacerbations: A Randomized, Double-Blind, Clinical Trial

Objective. To compare racemic albuterol (RAC) with levalbuterol (LEV) in continuous form for the treatment of acute pediatric asthma exacerbations in the emergency department. Study design. Children between the ages of 6 and 17 inclusive were enrolled if they had a history of asthma, presented to the emergency department with an acute asthma exacerbation, and had an initial forced expiratory volume in 1 second (FEV1) <70% predicted. Patients were then randomized to receive either 7.5 mg of RAC or 3.75 mg of LEV over 1 hour, in addition to standard asthma therapies. Spirometry and asthma scoring were performed at the end of the first hour, and a second hour-long nebulization with the same drug was administered if deemed necessary. Spirometry and asthma scoring were again performed and the final disposition was recorded. As a second, optional part of the study, baseline serum albuterol levels were collected on some patients before treatment. Results. A total of 99 patients completed the study (44 RAC and 55 LEV). Baseline characteristics were similar except that the RAC group had a higher baseline asthma score. Children in the RAC group had a greater improvement in their FEV1 (p = .043) as well as in their asthma scores (p = .01) after 1 hour of continuous treatment compared to the LEV group. The greater improvement in asthma scores was maintained after the second hour of continuous therapy in the RAC group (p = .008) but not for FEV1 measurements (p = .57). There were no differences between groups for changes in heart rate, respiratory rate, oxygen saturation, or rates of admission. Conclusions. At the doses used, RAC appears to be superior to LEV with respect to changes in FEV1 and asthma score. There was no significant difference between the drugs with respect to admission rates or side-effect profile.

Value of the Bronchodilator Response in Assessing Controller Naïve Asthmatic Children

Galant SP, Morphew T, Amaro S, Liao O. J Pediatr. 2007;151(5):457–462 PURPOSE OF THE STUDY. To define the bronchodilator response (BDR) cutoff point that best identified asthma to determine the frequency of abnormal spirometry results across severity. STUDY POPULATION. Children with asthma (n = 346) and 51 children without asthma, aged 4 to 17 years, who met entry criteria for spirometry were identified. METHODS. Controller-naive children were evaluated with clinical criteria alone to establish a diagnosis of asthma and severity classification and then compared with the BDR, which was calculated as the percentage change from the initial forced expiratory volume in 1 second (FEV1). Receiver operator characteristic analysis determined the cutoff point for asthma diagnosis that gave the best combination of sensitivity and specificity. RESULTS. The mean BDR in asthmatic subjects was 8.6% (95% confidence interval: 7.5%–9.8%), compared with 2.2% (95% confidence interval: 0.2%–4.3%) for the nonasthmatic subjects (P &amp;lt; .001). A BDR of ≥9% best differentiated these populations with a sensitivity rate of 42.5% and a specificity rate of 86.3%. Abnormal spirometry results, defined as a BDR of ≥9%, an FEV1 of &amp;lt;80% predicted, or both, ranged from 44.4% for mild-intermittent bronchial asthma to 57.0% for severe-persistent bronchial asthma. CONCLUSIONS. Spirometric criteria that include BDR can potentially identify children who have clinically mild asthma and might benefit from controller therapy. REVIEWER COMMENTS. What a breath of fresh air (pardon the pun). Establishing a firm diagnosis of asthma in pediatric patients can be, at times, a real challenge. Clinical history, physical examination, and a low FEV1 are all very useful in the diagnosis, but there are convincing data in children showing that an isolated, baseline FEV1 is not a good measure of the presence of asthma or its severity. The findings from this investigation demonstrate that detecting bronchodilator responsiveness (ie, 9% cutoff value for improvement in FEV1 after inhaled albuterol by metered-dose inhaler or nebulizer) can certainly aid in the diagnosis of asthma in children. A prospective assessment of this cutoff value in an unselected cohort of subjects, as well as the use of a single delivery system for the inhaled albuterol, will need to be investigated further to establish this measure as a useful diagnostic test for asthma in pediatric patients. Ultimately, use of the BDR in combination with baseline FEV1 should help clinicians detect a population of children with asthma and which children would benefit the most from therapeutic interventions such as inhaled corticosteroids.

Comparação da variação de resposta ao broncodilatador através da espirometria em portadores de asma ou doença pulmonar obstrutiva crônica

Making the differential diagnosis between asthma and chronic obstructive pulmonary disease (COPD) based on the response to inhaled bronchodilators by means of spirometry is controversial. The objective of this study was to identify the most useful spirometric variables in order to distinguish between asthma and COPD. Retrospective study conducted from April of 2004 to January of 2006, comparing the spirometric parameters of 103 nonsmoking patients with asthma to those of 108 patients with COPD who were smokers for more than 10 pack-years. All of the patients included in the study were older than 40 and presented stable disease at the time of the test. Initial forced expiratory volume in one second (FEV1) was the same in the two groups (pre-bronchodilator VEF1 = 51%). However, patients with COPD were older (66 +/- 9 years vs. 59 +/- 11 years, p < 0.001) and more frequently male (73 vs. 27%, p < 0,001).After the use of the bronchodilator, the median absolute difference in FEV1 was 0.25 L (range, -0.09 to 1.13 L) in patients with asthma and 0.09 L (range, -0.1 to 0.73 L) in those with COPD (p < 0.001). The highest sensitivity (55%), specificity (91%) and likelihood ratio (6.1) for asthma diagnosis was obtained when the percentage increase in postbronchodilator FEV1 in relation to the predicted FEV1 (Delta%prevVEF1) was equal to or greater than 10%. Isolated significant increases in forced vital capacity were more common in patients with COPD. In patients over the age of 40 and presenting obstructive lung disease, a Delta%prevVEF1 >or= 10% is the best spirometric parameter to distinguish asthma from COPD.

Clinical Significance of Plasma and Serum Vascular Endothelial Growth Factor in Asthma

Background. Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodeling in asthma. Purpose. We investigated whether VEGF levels are elevated in plasma and serum obtained from patients with asthma and evaluated whether levels of plasma VEGF correlated with those of serum VEGF. Methods. We measured levels of plasma and serum VEGF in patients with stable asthma or with acute asthma and examined the correlation between plasma and serum VEGF concentration with initial forced expiratory volume in 1 second (FEV1). Results. We found that levels of VEGF in plasma or in serum were significantly increased in stable asthmatic patients and even higher in acute asthmatic patients compared with the levels in healthy control subjects. The levels of serum VEGF correlated significantly with those of plasma VEGF. Additionally, the circulating VEGF levels were significantly inversely correlated with the percent predicted FEV1. Conclusion. These results suggest that the overproduction of VEGF is implicated in asthma exacerbation and that measurement of either plasma or serum VEGF level can be a valid index in asthmatic patients. Therefore, the changes in the VEGF levels in peripheral blood of asthmatic patients can be used as a measure for progression of asthma during treatment.

Value of the Bronchodilator Response in Assessing Controller Naïve Asthmatic Children

To define the bronchodilator response (BDR) cutoff point that best identified asthma to determine the frequency of abnormal spirometry results across severity. Controller naïve children were evaluated with clinical criteria alone to establish a diagnosis of asthma and severity classification, then compared with the BDR, which was calculated as the percent change from the initial forced expiratory volume in 1 second. Receiver operator characteristic analysis determined the cutoff point for asthma diagnosis that gave the best combination of sensitivity and specificity. Children with asthma (n = 346) and 51 children without asthma, aged 4 to 17 years, who met entry criteria for spirometry were identified. The mean BDR in asthmatics was 8.6% (95% CI, 7.5-9.8), compared with 2.2% (95% CI, 0.2-4.3) for non-asthmatics (P < .001). A BDR > or = 9% best differentiated these populations with a sensitivity rate of 42.5% and a specificity rate of 86.3%. Abnormal spirometry results, defined as a BDR > or = 9%, a forced expiratory volume in 1 second < 80% predicted, or both, ranged from 44.4% for mild intermittent bronchial asthma to 57.0% for severe persistent bronchial asthma. Spirometric criteria that include BDR can potentially identify children who have clinically mild asthma and might benefit from controller therapy.

Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial

Background: Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial,...

Serum Levels of Interleukins (IL)-4, IL-5, IL-13, and Interferon-γ in Acute Asthma

T-cell activation and alteration of cytokine levels are involved in the pathogenesis of bronchial asthma. However, the profile of circulating T-lymphocyte subsets and related cytokines during acute asthmatic attacks is still unclear. We hypothesized that serum levels of interleukin (IL)-4, IL-5, and IL-13 would be increased, whereas IFN-γ would be decreased in acute asthma. The subjects enrolled in this study included 58 acute asthmatics, 22 asymptomatic asthmatics, and 10 healthy controls. Serum levels of IL-4, IL-5, IL-13, and IFN-γ were measured using a sandwich enzyme-linked immunosorbent assay. We correlated serum levels of IL-4, IL-5, IL-13, and IFN-γ with initial forced expiratory volume in 1 sec (FEV1). Compared with control subjects, acute asthmatics had significantly increased levels of circulating IL-4 (p < 0.001), IL-5 (p < 0.001), and IL-13 (p < 0.001), although the differences were of borderline significance in serum IFN-γ (p = 0.069). There were also significant differences in the circulating levels of IL-4, IL-5, and IL-13 between acute asthmatics and asymptomatic asthmatics. There was no significant association between initial FEV1 and serum levels of IL-4 or IL-13, however, among acute asthmatics, a lower initial FEV1 was associated with higher IL-5 and/or lower IFN-γ levels. Our results suggest that serum levels of IL-4, IL-5, and IL-13 may be elevated in acute asthma, and that higher levels of IL-5 and/or lower levels of IFN-γ are associated with severe airway obstruction.

Addition of Salmeterol Versus Doubling the Dose of Beclomethasonein Children with Asthma

Verberne A, Frost C, Duiverman EJ, Grol MH, Kerrebijn KFAm J Respir Crit Care Med.1581998213219In studies involving adults, the addition of salmeterol to moderate doses of inhaled corticosteroids (ICS) led to better control of asthma symptoms, increased peak flow, and decreased diurnal variation in peak flow values. This study sought to compare the effects of 1 year of treatment with a moderate dose of an inhaled steroid, the same dose of the steroid with added salmeterol, and a doubling dose of an inhaled steroid in children with moderate asthma.There were 177 children enrolled in the study. The children were 6 to 16 years old and all had moderate to severe asthma. The initial forced expiratory volume in 1 second (FEV1) was between 55% to 90% of predicted and increased at least 10% after the use of inhaled albuterol. All participants also had a positive methacholine challenge, stable asthma, and were on 200 to 800 μg of an ICS for at least 3 months before study entry.The study was double-blinded and randomized. After a 6-week run-in period, there were 54 weeks of active treatment and a follow-up observation 2 weeks later. All patients were given beclomethasone dipropionate (BDP) 200 μg twice a day. Patients were randomized to receive either salmeterol 50 mcg, BDP 200 μg, or a placebo twice a day. At each clinic visit the children had their height and weight checked. Pulmonary functions were monitored at each visit. Compliance was checked by counting the number of blisters remaining on the medication cards. Diaries were kept with records of symptoms, rescue medication use, and peak flow values.The baseline characteristics of all three treatment groups were similar with regard to sex, age, height, duration of asthma, allergic status, ICS use, and initial FEV1. Compliance was slightly better in the BDP + salmeterol group—94% of doses were taken. At the end of the 54-week treatment period, there was no significant difference found between the treatment groups for the FEV1. There was still no difference found when the results were analyzed according to presenting dose of ICS, duration of use, baseline FEV1, methacholine sensitivity, and symptom scores. When airway responsiveness to methacholine was evaluated, it was found that all treatment groups had improved; however, the type of treatment made no difference. All treatment groups had improved peak flow values, but there was a more significant change observed in the BDP + salmeterol group during the first few months of the study. There was no difference between the treatment groups in day to day peak flow variability. Symptom control was better in all but there was no difference between the treatment groups. Growth was significantly slower in the BDP-800 μg/day group at 3.6 cm over the study period (BDP 400 group-4.5 cm and BDP + salmeterol group-5.1 cm).The addition of salmeterol to BDP or the doubling of the BDP dose in children with moderate asthma resulted in no difference in airway caliber, airway responsiveness, symptom scores, or exacerbation rates of asthma when compared with BDP 200 μg bid alone in children over the year of the study. The authors also conclude that rigorous monitoring and frequent visits help with medication compliance and subsequent improvement in disease activity. They also warn of the need to balance the antiinflammatory effect of higher doses of ICS against the effects on growth in children.The adult literature would have us believe that salmeterol may offer significant improvement in children who have moderate asthma. This study has shown that salmeterol does not offer any significant degree of improvement and more importantly it also shows that increased ICS doses also do not provide any significant differences either. Could it be that in this type of asthma clinical outcomes are optimized not so much by the doses and mixtures of therapies, but more by monitoring, frequent evaluations, and making sure that the children adhere to the treatment program?

Addition of Salmeterol Versus Doubling the Dose of Beclomethasonein Children with Asthma

1. Verberne A, 2. Frost C, 3. Duiverman EJ, 4. Grol MH, 5. Kerrebijn KF (1998) Am J Respir Crit Care Med. 158:213–219. [OpenUrl][1][PubMed][2][Web of Science][3] #### Purpose of the Study In studies involving adults, the addition of salmeterol to moderate doses of inhaled corticosteroids (ICS) led to better control of asthma symptoms, increased peak flow, and decreased diurnal variation in peak flow values. This study sought to compare the effects of 1 year of treatment with a moderate dose of an inhaled steroid, the same dose of the steroid with added salmeterol, and a doubling dose of an inhaled steroid in children with moderate asthma. ##### Study Population There were 177 children enrolled in the study. The children were 6 to 16 years old and all had moderate to severe asthma. The initial forced expiratory volume in 1 second (FEV1) was between 55% to 90% of predicted and increased at least 10% after the use of inhaled albuterol. All participants also … [1]: {openurl}?query=rft.jtitle%253DAmerican%2BJournal%2Bof%2BRespiratory%2Band%2BCritical%2BCare%2BMedicine%26rft.stitle%253DAm.%2BJ.%2BRespir.%2BCrit.%2BCare%2BMed.%26rft.issn%253D1073-449X%26rft.aulast%253DVERBERNE%26rft.auinit1%253DA.%25A0A.%25A0P.%25A0H.%26rft.volume%253D158%26rft.issue%253D1%26rft.spage%253D213%26rft.epage%253D219%26rft.atitle%253DAddition%2Bof%2BSalmeterol%2Bversus%2BDoubling%2Bthe%2BDose%2Bof%2BBeclomethasone%2Bin%2BChildren%2Bwith%2BAsthma%26rft_id%253Dinfo%253Apmid%252F9655732%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=9655732&link_type=MED&atom=%2Fpediatrics%2F104%2FSupplement_2%2F382.3.atom [3]: /lookup/external-ref?access_num=000074730700035&link_type=ISI

Pilot Study of Salbutamol in the Treatment of Acute Asthma – Little Apparent Benefit to Dose and Frequency Adjustments

STUDY OBJECTIVE: To compare two dosing regimens of salbutamol in acute asthma.DESIGN: Prospective randomized double-blind trial.SETTING: Urban emergency department.TYPE OF PARTICIPANTS: Patients who presented to the emergency department with moderate to severe asthma.INTERVENTIONS: All patients had pulmonary function testing and were randomized to group A (control; n=25) or group B (experimental; n=23). Group A (control) patients received salbutamol 2.5 mg delivered by wet aerosol at 0, 1 and 2 h (total dose 7.5 mg). At 20, 40, 80 and 100 mins a placebo aerosol was given. Group B patients received salbutamol 5 mg at 0 min and one-third the initial dose every 20 mins for a total of six doses by wet aerosol (total dose 15 mg).RESULTS: There were no differences in age, sex, preadmission medications or initial forced expiratory volume in 1 s (FEV1) between the groups. Forty-eight patients completed the study. Both groups of patients improved with mean absolute change in FEV1of 700 mL in group A and 590 mL in group B. There were no statistical differences between the two groups in terms of treatment response, admission rates or side effects.CONCLUSIONS: This study of patients presenting with acute asthma demonstrated no differences in improvement during the initial 3 h of treatment with a standard dose of aerosolized salbutamol given at hourly intervals (total dose 7.5 mg) compared with a higher total dose given at 20 min intervals (total dose 15 mg).

Long term effects of smoking on physical fitness and lung function: a longitudinal study of 1393 middle aged Norwegian men for seven years

To study association between smoking habits and long term decline in physical fitness and lung function in middle aged men who remained healthy. Baseline and follow up measurements performed during 1972-5 and 1980-2 respectively. National University Hospital of Oslo, Norway. 1393 men aged 40-59 at baseline who were all healthy at baseline and at follow up. Forced expiratory volume in one second and physical fitness (defined as total work done during a symptom limited bicycle ergometer test divided by body weight. Initial fitness was substantially lower among 347 persistent smokers than among 791 persistent non-smokers (1349 J/kg v 1618 J/kg), as was initial forced expiratory volume (3341 ml v 3638 ml). Mean (95% confidence interval) decline in fitness over 7.2 years was 217 (185 to 249) J/kg among smokers compared with 86 (59 to 113) J/kg among non-smokers (P < 0.001). Corresponding declines in forced expiratory volume were 271 (226 to 316) ml in smokers and 116 (85 to 147) ml in non-smokers (P < 0.001). Differences between smokers and non-smokers remained practically unchanged after adjustment for age and level of physical activity. Changes in fitness and forced expiratory volume among 199 men who had stopped smoking mimicked the findings for persistent non-smokers, and 56 men who started smoking presented findings close to those of persistent smokers. Decline in physical fitness and lung function among healthy middle aged men was considerably greater among smokers than among non-smokers and could not be explained by differences in age and physical activity.

A randomized, controlled comparison of isoetharine and albuterol in the treatment of acute asthma

To determine whether treatment of acute asthma with repeated doses of nebulized albuterol leads to greater bronchodilation and lower hospital admission rate than treatment with nebulized isoetharine. Randomized, double-blinded, controlled trial of albuterol and isoetharine. Patients between 18 and 50 years old presenting with acute asthma. Patients were excluded if they had a history of sensitivity to the study drugs, had congestive heart failure or chronic-obstructive pulmonary disease, or were unable to perform spirometry. One hundred three patients were entered into the study. All patients received oxygen and methylprednisolone in addition to administration of either isoetharine or albuterol. The nebulized aerosol was given at hourly intervals for a total of three doses. Spirometry was performed before treatment and again at 90 and 180 minutes. Initial forced expiratory volume at one minute (FEV1) was 38.1% of predicted normal for the albuterol group and 36.0% of predicted normal for the isoetharine group. At 180 minutes, FEV1 was 55.6% of predicted normal for the albuterol group and 57.1% of predicted for the isoetharine group (NS). Twenty-eight percent of the albuterol group required admission compared with 26% of the isoetharine group (NS). There was no difference in occurrence of side effects between the two groups. Repeated doses of albuterol do not lead to a greater improvement in pulmonary function or a lower hospital admission rate than treatment with isoetharine.