Increased Lung Function Research Articles

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

WS14.5 Exercise testing as a supplementary measure to assess the benefit of intravenous antibiotic courses

Objectives The use of intravenous antibiotics has long been established as the treatment for respiratory exacerbations in patients colonised with Pseudomonas aeruginosa. However improvements in spirometry are not always demonstrated following treatment. Patients often place significant importance on these readings and may doubt the benefit of treatment if an increase in lung function is not seen. A small study comparing the results of exercise test results with spirometry at the start and end of a course of intravenous antibiotics to see if they could be used as a supplementary measure to assess the benefit of treatment. Methods 27 patients (63% male; mean age 35 yrs, range 17–70; mean % FEV1 45.7%, range 17–86%) who were admitted for a two week course of intravenous antibiotics were approached to check their lung function and exercise tolerance at the start of their admission. 18 patients agreed and 9 declined. The tests were then repeated at the end of the hospital admission. The incremental shuttle walk test and the 6 minute walk test were used depending on patient preference. Results 10 patients (55%) show improvement in both their spirometry and exercise tolerance, however 8 patients (45%) demonstrated less than a 2% increase in their lung function; 3 recording a lower value than at the start of treatment. Of these 8 patients, 7 showed improvements in their exercise test results, mean 48.6%, range 7.6–85%. Conclusion Exercise testing as a supplementary measure to assess the benefit of intravenous antibiotic therapy may be of value, particularly in patients who do not show an improvement in spirometry.

321 Changes in lung function and airway microbiology following ivacaftor therapy in an adult G551D homozygote

Objectives Ivacaftor has increased lung function and decreased pulmonary exacerbations and intravenous antibiotic use in patients with CF carrying the G551D mutation. This case study describes the effects of ivacaftor on airway microbiology and lung function in a G551D homozygote with chronic Pseudomonas aeruginosa (PA) infection. Methods All sputum culture reports prior to ivacaftor therapy were reviewed. Following ivacaftor initiation sputum samples were sent for standard culture at each clinic visit. 16S gene rRNA pyrosequencing was performed on paired sputum samples collected immediately prior to and after 6 months of ivacaftor therapy. FEV 1 was measured at baseline and at each follow up visit. Sweat chloride was assessed pre-treatment and at 6 months. Results Mucoid PA infection was acquired in 1983. The pre-ivacaftor baseline sputum sample and all preceding 26 samples taken over 8 years were culture positive for PA. 7 consecutive samples collected over 16 months following ivacaftor were culture negative for PA. A later sample was culture positive for the original infecting strain of PA (using variable number tandem repeat profiling). 16S gene rRNA pyrosequencing showed a drop in relative abundance of PA from 98.2% to 4.8% and an increase in microbial diversity over the 6 month sample period. FEV 1 improved from 68% predicted (baseline) to 90% predicted (20 months post ivacaftor). Sweat chloride reduced from 105 mmol/L (baseline) to 52 mmol/L (6months). Conclusion Bacterial diversity and relative abundance of typical CF pathogens may be significantly altered by modulation of both CFTR alleles. Sputum culture clearance of mucoid PA on should be interpreted with caution.

113 Inhalative meropenem–tobramycin–colistin combination improves lung function in chronic Pseudomonas aeruginosa colonization

Objectives Pseudomonas aeruginosa in the airways of CF-patients restricts the efficacy of antibiotics leading to chronic infections which have a large impact on morbidity and mortality. Antibiotic combination therapy might be more efficient than single antibiotics to combat lung infections in CF. Methods In an observational pilot study CF patients, suffering from chronic P. aeruginosa lung infection, pre-treated either with tobramycin or colistin, were inhalatively treated for 28 days with 300 mg tobramycin in combination with colistin (1 Mio IU) and meropenem 250 mg twice daily. Lung function expressed as expiratory volume in 1 second (FEV 1 ), bacterial cfu and adverse events were determined before and after treatment. Results 15 adult CF patients (mean age 27.9±9.4 years) inhaled b-sympathomimetics prior to the triple antibiotic solution which was well tolerated by all patients. FEV1 increased significantly by 7.8±5.7% absolute and 11.6±10% relative to baseline (p = 0.001) since only one patient showed no benefit after 28 days of inhalation. P. aeruginosa decreased significantly by 1.46±1.4 log cfu/ml (p = 0.042). No adverse reactions were found. Conclusion For the first time administered, the efficacy of an inhalative triple antibiotic solution with meropenem, tobramycin and colistin suggest, that this combination therapy seems to be safe and efficient to increase lung function and decrease chronic Pseudomonas infection in CF patients. This alternative combination of inhalative antibiotics has to be investigated in further trials.

Stents for Bronchial Stenosis After Lung Transplantation: Should They Be Removed?

BackgroundAirway complications after lung transplantation are the major cause of morbidity, affecting up to 33% of all cases. Bronchial stenosis is the most common complication. The use of stents has been established as the most effective therapy; however, their removal is recommended after 3–6 months of use. We have been using self-expandable stents as a definitive treatment and remove them only if necessary. For this report, we evaluated the use of self-expandable stents as a definitive treatment for bronchial stenosis after lung transplantation. MethodsWe performed a retrospective cohort study to evaluate patients with bronchial stenosis from August 2003 to April 2014. Clinical and pulmonary function test data were collected. ResultsTwo hundred lung transplants were performed, 156 of which were bilateral. Sixteen patients experienced airway complications: 4 had dehiscence, 2 necrosis, and 10 bronchial stenosis. Of these patients, 7 had undergone bilateral procedures, and 2 patients developed stenosis in both sides. Twelve anastomotic stenoses were observed. The follow-up after stenting ranged from 1 to 7 years. All patients had increased lung function, and 4 remained stable with sustained increase in pulmonary function without episodes of infection. Three patients required removal of their prosthesis 6 months to 1 year after implantation because of complications. Two patients died owing to unrelated causes. ConclusionsDefinitive treatment of bronchial stenosis with self-expandable stents is a viable option. The 1st year seems to be the most crucial for determining definitive treatment, because no patients required removal of their stent after 1 year.

What Is the Role of Tiotropium in Asthma?: A Systematic Review With Meta-analysis

The role of tiotropium for the treatment of asthma has not yet been clearly defined. The aim of this systematic review was to assess the efficacy and safety of tiotropium in patients with asthma. Randomized placebo-controlled trials were included. Primary outcomes were peak and trough FEV1 and morning and evening peak expiratory flow (PEF). Thirteen studies (4,966 patients) were included. Three different therapeutic protocols were identified. Tiotropium as an add-on to inhaled corticosteroids (ICSs) showed statistically and clinically significant increases in PEF (22-24 L/min) and FEV1 (140-150 mL). Additionally, tiotropium decreased the rate of exacerbations (number needed to treat for benefit [NNTB], 36) and improved asthma control. The use of tiotropium in patients poorly controlled despite the use of medium to high doses of ICS was not inferior to salmeterol. Finally, the use of tiotropium as an add-on to ICS/salmeterol combination increased pulmonary function to a clinically significant magnitude, reduced asthma exacerbations (relative risk, 0.70; 95% CI, 0.53-0.94; P < .02; I2 = 0%; NNTB, 17), and improved asthma control compared with ICS/salmeterol. Tiotropium was well tolerated, and no potential safety signals were observed. Tiotropium resulted noninferiorly to salmeterol and superiorly to placebo in patients with moderate to severe asthma who were not adequately controlled by ICS or ICS/salmeterol. Major benefits were concentrated in the increase in lung function and in the case of patients with severe asthma, in the reduction of exacerbations.

New perspectives in therapy of chronic obstructive pulmonary disease: revolving around aclidinium bromide

Aclidinium is a new anticholinergic agent for maintenance therapy of chronic obstructive pulmonary disease (COPD). Pharmacokinetic properties of aclidinium provide higher safety profile and lower risk of extrapulmonary adverse effects. In clinical phase III studies, aclidinium significantly increased lung function, reduced clinical symptoms and improved quality of life in patients with COPD. The aim of this review was to analyze clinical trials evaluating pharmacokinetics, clinical efficacy and safety of inhaled aclidinium bromide.

ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy

In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients. We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement. High baseline levels of ACE correlated significantly with lung function improvement after treatment (R=0.45, p<0.0001; stronger in the pulmonary subgroup R 0.57, p<0.0001). ACE baseline levels >90U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2U/l (p<0.0001) and sIL-2R with 1850pg/ml (p<0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R=0.63, P<0.0001; sIL-2R R=0.56, P<0.0001). Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients.

Effects of inhaled bronchodilators on lung function and cycling performance in female athletes with and without exercise-induced bronchoconstriction.

Inhaled β2-agonists may cause differential effects on lung function and athletic performance in female compared to male athletes. The objective of this study was to compare the effects of inhaled β2-agonists on lung function and cycling performance between female athletes with and without exercise-induced bronchoconstriction and with previously published data on men. Double-blind crossover randomized controlled trial. Twenty-one female athletes (6 with exercise-induced bronchoconstriction and 15 without exercise-induced bronchoconstriction) performed a simulated 10-km time-trial on a cycle ergometer 60 min after the inhalation of either 400 μg of salbutamol or placebo. Forced expiratory volume in 1s, was measured immediately before and 30 min after inhalation. Performance was measured by mean power output over the duration of the time trial. After salbutamol inhalation, Forced expiratory volume in 1s improved significantly in athletes with exercise-induced bronchoconstriction (M (SD) = 6.1% (47.6)) and athletes without exercise-induced bronchoconstriction (4.0% (3.1); p ≤ 0.02). Mean power output was significantly decreased after salbutamol use (204 W (21)) compared to placebo (208 W (17); p = 0.047), regardless of airway hyperresponsiveness. Relative to placebo, salbutamol significantly increased mean oxygen consumption (46.9 mL kg(-1)min(-1) (5.9) vs. 44.8 mL kg(-1)min(-1) (4.0); p = 0.049) and significantly decreased cycling economy (72.8 W L(-1)min(-1) (6.8) vs. 76.4 W L(-1)min(-1) (4.3); p = 0.01). The inhalation of salbutamol induced a significant increase in lung function in female athletes, but this increased lung function did not translate to improved exercise performance.

Healthy Eating Index 2005 and selected macronutrients are correlated with improved lung function in humans

A number of dietary components have been associated with lung function. However, a comprehensive measure of a healthy diet has not been compared with lung function. Herein, we test the hypothesis that a healthy overall diet, as assessed by the Healthy Eating Index 2005 (HEI-2005), will be associated with increased lung function. This is an investigation using the Atherosclerosis Risk in Communities Research Materials obtained from the National Heart Lung Blood Institute. The study surveyed dietary habits of 15 567 American subjects from 4 communities in 1987 to 1990. Spirometric measures of lung function were also taken at entry to the study and a second time 3 years later. Based on food and nutritional data collected by food frequency questionnaire, an HEI-2005 score was calculated for each subject. This total score, together with its 12 components scores and associated macronutrient, was compared with lung function results by linear regression. Models were controlled for smoking behavior, demographics, and other important covariates. The HEI-2005 total scores were positively associated with forced expiratory volume in 1 second per forced vital capacity (FEV(1)/FVC) at visit 1 (β = .101 per increase in 1 quintile of HEI-2005) and visit 2 (β = .140), and FEV(1) as percentage of the predicted FEV(1) at visit 2 (β = .215) (P < .05). In addition, HEI-2005 component scores that represented high intakes of whole grains (β = .127 and .096); saturated fats (β = −.091); and solid fats, alcohol, and added sugar (β = −.109 and −.131) were significantly associated with FEV(1)/FVC at either visit 1 or visit 2. Intakes of total calories (β =−.082 at visit 1) and saturated fatty acids (β = −.085 at visit 2) were negatively associated with FEV(1)/FVC. Dietary polyunsaturated fatty acids (β = .085 and .116) and long-chain omega-3 fatty acids (β = .109 and .103), animal protein (β = .132 and .093), and dietary fiber (β = .129) were positively associated with lung health. An overall healthy diet is associated with higher lung function.

P193 A role for active Vitamin D in steroid resistant asthma patients who have enhanced production of IL-17A and reduced IL-10

BackgroundSteroid refractory (SR) asthma, a distinct disease phenotype, has a high morbidity and mortality and takes up a disproportional burden of healthcare cost. IL-17A is a pro-inflammatory cytokine that is...

Correlation of increased PARP14 and CCL26 expression in biopsies from children with eosinophilic esophagitis

Correlation of increased PARP14 and CCL26 expression in biopsies from children with eosinophilic esophagitis

Inhaled salbutamol does not affect athletic performance in asthmatic and non-asthmatic cyclists

RationaleSalbutamol may affect lung function and exercise performance differently in individuals with and without asthma.ObjectivesTo compare the effects of inhaled salbutamol on lung function, exercise performance and respiratory parameters during...

Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis

A major purpose of treating patients with cystic fibrosis (CF) is to prevent or delay chronic lung infections with CF-pathogenic Gram-negative bacteria. In the intermittent stage, bacteria can usually be eradicated from the lungs with antibiotics, but following eradication, the next lung colonisations often occur with bacteria of identical genotype. This may be due to re-colonisation from the patient's paranasal sinuses. In our study, we found that approximately two-thirds of CF patients having sinus surgery (FESS) had growth of CF-lung-pathogenic Gram-negative bacteria in their sinuses (Pseudomonas aeruginosa, Achromobacter xylosoxidans, Burkholderia cepacia complex). The environment in the sinuses is in many ways similar to that of the lower respiratory tract, e.g. low oxygen concentration in secretions. Sinus bacteria are more difficult to eradicate than in the lungs, thus, having good conditions for adapting to the environment in the lungs. In the presence of bacteria, the environment of the sinuses differs from that of the lower respiratory tract by having a higher immunoglobulin A (IgA): IgG ratio, and reduced inflammation. We found a significant correlation between the concentration of IgA against P. aeruginosa (standard antigen and alginate) in nasal secretions and saliva and CF patients' infection status (not lung colonised, intermittently colonised or chronically lung-infected with P. aeruginosa). This supports the hypothesis that infections often originate in the sinuses and can be a focus for initial lung colonisation or for maintaining lung infections in CF patients. We are confident that anti-P. aeruginosa IgA can be used as an early supplementary tool to diagnose P. aeruginosa colonisation; P. aeruginosa being the microorganism causing most morbidity and mortality in CF patients. This is important since urgent treatment reduces morbidity when CF patients are early colonised with P. aeruginosa, however, there is a lack of diagnostic tools for detecting the early colonisation in the lungs and in the sinuses. We initiated a treatment strategy for CF patients to prevent sino-nasal bacteria being seeded into the lower airways: we recommended extensive functional endoscopic FESS with creation of sufficient drainage from all involved sinuses with subsequent i.v. antibiotics and at least 6 months of twice daily nasal irrigation with saline and antibiotics. By this strategy, sinus bacteria could be eradicated in a large proportion of patients. Essentially, growth of CF-pathogenic bacteria from the lower respiratory tract was decreased following the treatment. Furthermore, a number of patients have been free from CF-pathogenic bacteria for more than one year after FESS, and thus re-classified as "not lung colonised". We also corroborated that CF patients obtain an improved quality of life and reduction in their symptoms of chronic rhinosinusitis after FESS. It is primarily intermittently lung colonised CF patients with CF-pathogenic bacteria in their sinuses that seem to benefit from the treatment strategy. This is in accordance with the fact that we did not see a significant increase in lung function and only a small decrease in specific antibodies after FESS; a high systemic immune and inflammatory response and a decreasing lung function is generally not present in patients who primarily have sinus CF-pathogenic bacteria. It is important that guidelines are created for how CF patients with CF-pathogenic bacteria in the sinuses are to be treated, including criteria for who may likely benefit from FESS, and who may be treated exclusively with conservative therapy, e.g. saline and antibiotic irrigations.

Swimming training for asthma in children and adolescents aged 18 years and under

Swimming training for asthma in children and adolescents aged 18 years and under

Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis

Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment.

Swimming training for asthma in children and adolescents aged 18 years and under

Background Asthma is the most common chronic medical condition in children and a common reason for hospitalisation. Observational studies have suggested that swimming, in particular, is an ideal form of physical activity to improve fitness and decrease the burden of disease in asthma. Objectives To determine the effectiveness and safety of swimming training as an intervention for asthma in children and adolescents aged 18 years and under. Search methods We searched the Cochrane Airways Group's Specialised Register of trials (CENTRAL), MEDLINE , EMBASE, CINAHL, in November 2011, and repeated the search of CENTRAL in July 2012. We also handsearched ongoing Clinical Trials Registers. Selection criteria We included all randomised controlled trials (RCTs) and quasi-RCTs of children and adolescents comparing swimming training with usual care, a non-physical activity, or physical activity other than swimming. Data collection and analysis We used standard methods specified in the Cochrane Handbook for Systematic reviews of Interventions. Two review authors used a standard template to independently assess trials for inclusion and extract data on study characteristics, risk of bias elements and outcomes. We contacted trial authors to request data if not published fully. When required, we calculated correlation coefficients from studies with full outcome data to impute standard deviation of changes from baseline. Main results Eight studies involving 262 participants were included in the review. Participants had stable asthma, with severity ranging from mild to severe. All studies were randomised trials, three studies had high withdrawal rates. Participants were between five to 18 years of age, and in seven studies swimming training varied from 30 to 90 minutes, two to three times a week, over six to 12 weeks. The programme in one study gave 30 minutes training six times per week. The comparison was usual care in seven studies and golf in one study. Chlorination status of swimming pool was unknown for four studies. Two studies used non-chlorinated pools, one study used an indoor chlorinated pool and one study used a chlorinated but well-ventilated pool. No statistically significant effects were seen in studies comparing swimming training with usual care or another physical activity for the primary outcomes; quality of life, asthma control, asthma exacerbations or use of corticosteroids for asthma. Swimming training had a clinically meaningful effect on exercise capacity compared with usual care, measured as maximal oxygen consumption during a maximum effort exercise test (VO2 max) (two studies, n = 32), with a mean increase of 9.67 mL/kg/min; 95% confidence interval (CI) 5.84 to 13.51. A difference of equivalent magnitude was found when other measures of exercise capacity were also pooled (four studies, n = 74), giving a standardised mean difference (SMD) 1.34; 95% CI 0.82 to 1.86. Swimming training was associated with small increases in resting lung function parameters of varying statistical significance; mean difference (MD) for FEV1 % predicted 8.07; 95% CI 3.59 to 12.54. In sensitivity analyses, by risk of attrition bias or use of imputed standard deviations, there were no important changes on effect sizes. Unknown chlorination status of pools limited subgroup analyses. Based on limited data, there were no adverse effects on asthma control or occurrence of exacerbations. Authors' conclusions This review indicates that swimming training is well-tolerated in children and adolescents with stable asthma, and increases lung function (moderate strength evidence) and cardio-pulmonary fitness (high strength evidence). There was no evidence that swimming training caused adverse effects on asthma control in young people 18 years and under with stable asthma of any severity. However whether swimming is better than other forms of physical activity cannot be determined from this review. Further adequately powered trials with longer follow-up periods are needed to better assess the long-term benefits of swimming.

Dust exposure is associated with increased lung function loss among workers in the Norwegian silicon carbide industry

ObjectivesTo investigate the relationship between dust exposure and annual change in lung function among employees in Norwegian silicon carbide (SiC) plants using a quantitative job exposure matrix (JEM) regarding total...

Lung function decline in children and adolescents post-infectious bronchiolitis obliterans: a prospective long term cohort study

Aim of this paper was to evaluate the effects of changes in obesity status on lung function decline over an 8-year follow-up.Adults over 24 years (n=1212) from the general population, who participated in both Po River Delta first (PD1, 1980–1982) and second (PD2, 1988–1991) epidemiological surveys, were stratified as “never obese” (BMI<30 Kg/m2 at both PD1 and PD2), “becoming obese” (BMI<30 Kg/m2 at PD1 and ⩾30 Kg/m2 at PD2), “always obese” (BMI⩾30 Kg/m2 at both PD1 and PD2), and “becoming non-obese” (BMI⩾30 Kg/m2 at PD1 and <30 Kg/m2 at PD2). Linear regression models for changes in FEV1, FVC, and VC (computed as absolute differences between the values at PD2 and those at PD1) with longitudinal categories of obesity, gender, age, and baseline smoking habits as covariates were applied.The “becoming obese” and “always obese” categories had a significantly greater decline of lung function than “never obese” group; in the “always obese” group, this was true for vital capacities but not FEV1. Conversely, in the “becoming non-obese” group lung function was at PD2 improved with respect to PD1. Compared with “Never obese” the mean increase in lung function was of 93, 180, and 48 mL for FEV1, FVC, and VC, respectively.In this general population sample, remaining or becoming obese increases the decline in lung function over 8 years, while becoming non-obese decreases it.

Transient impact of omalizumab in pollen allergic patients undergoing specific immunotherapy

Recently, we showed that combination of omalizumab with specific immunotherapy (SIT) for treatment of patients with seasonal allergic rhinitis (SAR) and comorbid seasonal allergic asthma (SAA) is safe and reduced the symptom load in a statistically significant and clinically meaningful manner during the first pollen season. The aim of this study was to investigate long-lasting effects of an initial combination treatment with SIT+omalizumab, a monoclonal anti-IgE antibody, in a follow-up period with SIT treatment only in patients with SAR and comorbid SAA incompletely controlled by conventional pharmacotherapy. A randomized, double-blind, placebo-controlled, multicenter trial was performed to assess the efficacy and safety of omalizumab (Xolair(®)) vs. placebo in combination with SIT (depigmented allergoid vaccine, Depigoid(®)) during the first grass pollen season. Omalizumab or placebo therapy was started 2 wk before SIT; the whole treatment lasted 18 wk. After the first pollen season, SIT was given for two subsequent years without omalizumab. Primary end-point was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use in the second and third year. A total of 140 patients (age 11-46 yr) were randomized; 130, 128, and 114 patients finished the study after 1, 2, and 3 yr, respectively. The main efficacy variable was the mean daily symptom load as assessed in the patients' diary. No systematic differences between both analysis groups were detected in the findings from symptom load, symptom severity score, or rescue medication score. Further subjective data did not show differences between both groups in the quality-of-life data as assessed with the ACQ, AQLQ, and the RQLQ. Investigators' assessment of treatment effectiveness in the first and second year of study extension showed more patients with favorable long-term treatment outcome ('excellent' and 'good') in the SIT plus omalizumab group than in the SIT plus placebo group. In line with these findings, FEV1 improved at the end of both years in the group which was treated with the combination therapy in the double-blind study compared with the Depigoid plus placebo group. Eighteen weeks' treatment of omalizumab in combination with SIT in patients with SAR and comorbid SAA reduced the symptom load during the treatment period but showed no prolonged effect during treatment with SIT only. A slight increase in lung function (FEV1) in patients formerly treated with the omalizumab/SIT combination therapy should encourage further evaluation of long-term effects of omalizumab.