Community pharmacist counseling improves adherence and asthma control: a nationwide study.

BACKGROUND: Pharmaceutical counseling (PC) interventions have been shown to improve adherence to controller medication and asthma control. However, the real-life impact of these PC interventions in difficult-to-control asthma patients remains unclear. We aimed to assess the effectiveness of PC interventions in real life using nationwide claims data. METHODS: Demographics and drugs use of patients who received ICS in 2017 with or without pharmaceutical counseling were retrieved from a Belgian claims database. Asthma-related drug use from 1 year before first ICS dispensing in 2017 (reference period) was compared with 1 year after. Outcomes were usage of inhaled corticosteroids (ICS) in defined daily doses (DDD), proportion of users of short-acting beta-agonist (SABA), antibiotics, oral corticosteroids (OCS), asthma biologicals and controller-to-total (CTT) ratio. RESULTS: The study population consisted of difficult-to-control asthma patients aged 5-40 years with at least the first interview within 90 days after first ICS dispensing (n = 1350). ICS usage increased significantly in the year after PC intervention compared with the reference period (+ 43.3 DDD/patient, p < 0.05). A nominal decrease was observed in the proportion of SABA (48.0 to 46.2%) and antibiotics (54.5 to 52.7%) after PC intervention compared with the reference period. CTT ratio significantly increased from 0.671 to 0.749 (p < 0.05). The proportion of biological users was nominally lower in the intervention group compared with a control group (n = 50,477) in the post-intervention time period (0.22% versus 0.30%). CONCLUSIONS: This first nationwide study among difficult-to-control asthma patients suggests that community pharmacist counseling is effective in real life to improve controller adherence and asthma control.

Serum Th-2 cytokines and FEV1 decline in WTC-exposed firefighters: A 19-year longitudinal study.

BACKGROUND: Accelerated-FEV1 -decline, defined as rate of decline in FEV1 > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)-exposed firefighters. Accelerated-FEV1 -decline in this cohort is associated with elevated blood eosinophil concentrations, a mediator of Th-2 response. We hypothesized that an association exists between Th-2 biomarkers and FEV1 decline rate in those with accelerated-FEV1 -decline. METHODS: Serum was drawn from Fire Department of the City of New York (FDNY) firefighters 1-6 months (early) (N = 816) and 12-13 years (late) (N = 983) after 9/11/2001. Th-2 biomarkers IL-4, IL-13, and IL-5 were assayed by multiplex Luminex. Individual FEV1 decline rates were calculated using spirometric measurements taken: (1) between 9/11/2001 and 9/10/2020 for the early biomarker group and (2) between late measurement date and 9/10/2020 for the late biomarker group. Associations of early and late Th-2 biomarkers with subsequent FEV1 decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders. RESULTS: In WTC-exposed firefighters with accelerated-FEV1 -decline, IL-4, IL-13, and IL-5 measured 1-6 months post-9/11/2001 were associated with greater FEV1 decline ml/year between 9/11/2001 and 9/10/2020 (-2.9 ± 1.4 ml/year per IL-4 doubling; -8.4 ± 1.2 ml/year per IL-13 doubling; -7.9 ± 1.3 ml/year per IL-5 doubling). Among late measured Th-2 biomarkers, only IL-4 was associated with subsequent FEV1 decline rate (-4.0 ± 1.6 ml/year per IL-4 doubling). CONCLUSIONS: In WTC-exposed firefighters with accelerated-FEV1 -decline, elevated serum IL-4 measured both 1-6 months and 12-13 years after 9/11 is associated with greater FEV1 decline/year. Drugs targeting the IL-4 pathway may improve lung function in this high-risk subgroup.

Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long-acting beta agonists.

BACKGROUND: Greater than average loss of one-second forced expiratory volume (FEV1 ) is a risk factor for asthma, chronic obstructive pulmonary disease (COPD), and asthma/COPD overlap syndrome in World Trade Center (WTC)-exposed firefighters. Inhaled corticosteroids and long-acting beta agonists (ICS/LABA) are used to treat obstructive airways disease but their impact on FEV1 -trajectory in this population is unknown. METHODS: The study population included WTC-exposed male firefighters who were treated with ICS/LABA for 2 years or longer (with initiation before 2015), had at least two FEV1 measurements before ICS/LABA initiation and two FEV1 measurements posttreatment between September 11, 2001 and September 10, 2019. Linear mixed-effects models were used to estimate FEV1 -slope pre- and post-treatment. RESULTS: During follow-up, 1023 WTC-exposed firefighters were treated with ICS/LABA for 2 years or longer. When comparing intervals 6 years before and 6 years after treatment, participants had an 18.7 ml/year (95% confidence interval [CI]: 11.3-26.1) improvement in FEV1 -slope after adjustment for baseline FEV1 , race, height, WTC exposure, weight change, blood eosinophil concentration, and smoking status. After stratification by median date of ICS/LABA initiation (January 14, 2010), earlier ICS/LABA-initiators had a 32.5 ml/year (95% CI: 19.5-45.5) improvement in slope but later ICS/LABA-initiators had a nonsignificant FEV1 -slope improvement (7.9 ml/year, 95% CI: -0.5 to 17.2). CONCLUSIONS: WTC-exposed firefighters treated with ICS/LABA had improved FEV1 slope after initiation, particularly among those who started earlier. Treatment was, however, not associated with FEV1 -slope improvement if started after the median initiation date (1/14/2010), likely because onset of disease began before treatment initiation. Research on alternative treatments is needed for patients with greater than average FEV1 -decline who have not responded to ICS/LABA.

Low serum IgA and airway injury in World Trade Center-exposed firefighters: a 17-year longitudinal study.

Serum IgA ≤70 mg/dL (low IgA) is associated with exacerbations of chronic obstructive pulmonary disease. The association of low IgA with longitudinal lung function is poorly defined. This study included 917 World Trade Center (WTC)-exposed firefighters with longitudinal spirometry measured between September 2001 and September 2018 and IgA measured between October 2001 and March 2002. Low IgA, compared with IgA >70 mg/dL, was associated with lower forced expiratory volume in 1 s (FEV1) % predicted in the year following 11 September 2001 (94.1% vs 98.6%, p<0.001), increased risk of FEV1/FVC <0.70 (HR 3.8, 95% CI 1.6 to 8.8) and increased antibiotic treatment (22.5/100 vs 11.6/100 person-years, p=0.002). Following WTC exposure, early IgA ≤70 mg/dL was associated with worse lung function and increased antibiotic treatment.

Risk factors for post-9/11 chronic rhinosinusitis in Fire Department of the City of New York workers.

OBJECTIVES: Chronic rhinosinusitis (CRS) has high socioeconomic burden but underexplored risk factors. The collapse of the World Trade Center (WTC) towers on 11 September 2001 (9/11) caused dust and smoke exposure, leading to paranasal sinus inflammation and CRS. We aim to determine which job tasks are risk factors for CRS in WTC-exposed Fire Department of the City of New York (FDNY) firefighters and emergency medical services (EMS) workers. METHODS: This cohort study included a 16-year follow-up of 11 926 WTC-exposed FDNY rescue/recovery workers with data on demographics, WTC exposure, job tasks and first post-9/11 complete blood counts. Using multivariable Cox regression, we assessed the associations of WTC exposure, work assignment (firefighter/EMS), digging and rescue tasks at the WTC site and blood eosinophil counts with subsequent CRS, adjusting for potential confounders. RESULTS: The rate of CRS was higher in firefighters than EMS (1.80/100 person-years vs 0.70/100 person-years; p<0.001). The combination of digging and rescue work was a risk factor for CRS (HR 1.54, 95% CI 1.23 to 1.94, p<0.001) independent of work assignment and WTC exposure. CONCLUSIONS: Compared with EMS, firefighters were more likely to engage in a combination of digging and rescue work, which was a risk factor for CRS. Chronic irritant exposures associated with digging and rescue work may account for higher post-9/11 CRS rates among firefighters.

Biomarkers of patient intrinsic risk for upper and lower airway injury after exposure to the World Trade Center atrocity.

BACKGROUND: High rates of upper and lower airways disease have occurred in Fire Department of the City of New York (FDNY) workers exposed to the World Trade Center (WTC) disaster site. Most experienced acute declines in pulmonary function, and some continued to experience decline over 14 years of follow-up. Similarly, some with rhinosinusitis had symptoms requiring sinus surgery. AIM: To increase generalizability of biomarker investigation, we describe biomarkers of risk for upper and lower airway injury that do not require stored serum. METHODS: We review WTC biomarker literature. RESULTS: Cytokines expressed in stored serum from the first 6 months post-9/11 can identify individuals at higher risk for future abnormal pulmonary function. CONCLUSION: This research will help identify individuals at high risk of lung and sinus disease that develop after these, or future, irritant exposures for intensive monitoring and treatment. It may also identify targets for effective therapeutic interventions. Am. J. Ind. Med. 59:788-794, 2016. © 2016 Wiley Periodicals, Inc.

Determinants of poor inhaler technique and poor therapy adherence in obstructive lung diseases: a cross-sectional study in community pharmacies.

BACKGROUND: Correct inhaler use can be challenging in real life, with incorrect use resulting in poor symptom control. The aim of this study was to examine factors associated with poor inhaler technique and poor therapy adherence among patients with obstructive lung disease in community pharmacies. METHODS: A cross-sectional study was conducted in patients with obstructive lung diseases in nine Belgian community pharmacies. Logistic regression analyses identified factors associated with poor inhaler technique and poor therapy adherence (assessed by the Test of Adherence to Inhalers and the modified Medication Possession Ratio). RESULTS: Seventy obstructively impaired community patients (median age 64 y, 56% females) were included and the technique of 122 inhalers was assessed. Inhaler technique scored generally poor, with half of patients making critical errors in using at least one of their inhalers. In multivariable analysis, the use of multiple devices (adjusted OR, aOR 11.68; 95% CI 3.29 to 41.51) and a diagnosis of asthma-Chronic Obstructive Pulmonary Disease overlap (ACO; aOR 7.06; 95% CI 1.15 to 43.35), were associated with making critical errors in inhaler technique independent of quality of life. Non-adherence occurred in more than one-third of patients, and occurred in up to one half of the patients when also taking overuse into account. In multivariable analysis for therapy adherence, current smoking was associated with poor therapy adherence (aOR 0.15; 95% CI 0.02 to 0.96) independently of age and poor treatment knowledge. Therapy adherence was poor in patients with asthma compared with those with ACO. Current smokers and highly educated patients seemed to be at increased risk for inhaler overuse. CONCLUSIONS: Given the important role of a correct inhaler technique and therapy adherence in disease control, these findings emphasise the need for patient education and aiming uniformity in the inhaler device. TRIAL REGISTRATION NUMBER: B670201835229.

Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study.

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.

Abnormalities on Chest Computed Tomography and Lung Function Following an Intense Dust Exposure: A 17-Year Longitudinal Study.

Fire Department of the City of New York (FDNY) firefighters experienced intense dust exposure working at the World Trade Center (WTC) site on and after 11/9/2001 (9/11). We hypothesized that high-intensity WTC exposure caused abnormalities found on chest computed tomography (CT). Between 11/9/2001-10/9/2018, 4277 firefighters underwent a clinically-indicated chest CT. Spirometric measurements and symptoms were recorded during routine medical examinations. High-intensity exposure, defined as initial arrival at the WTC on the morning of 9/11, increased the risk of bronchial wall thickening, emphysema, and air trapping. Early post-9/11 symptoms of wheeze and shortness of breath were associated with bronchial wall thickening, emphysema, and air trapping. The risk of accelerated forced expiratory volume at one second (FEV1) decline (>64 mL/year decline) increased with bronchial wall thickening and emphysema, but decreased with air trapping. The risk of airflow obstruction also increased with bronchial wall thickening and emphysema but decreased with air trapping. In a previously healthy occupational cohort, high-intensity WTC exposure increased the risk for CT abnormalities. Bronchial wall thickening and emphysema were associated with respiratory symptoms, accelerated FEV1 decline, and airflow obstruction. Air trapping was associated with respiratory symptoms, although lung function was preserved. Physiologic differences between CT abnormalities suggest that distinct types of airway injury may result from a common exposure.

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure: A Longitudinal Study.

BACKGROUND: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined. METHODS: This study included 2,137 WTC-exposed firefighters who underwent a clinically indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001 and 9/10/2017. A post-BD FEV1 increase of > 12% and 200 mL from baseline defined asthma, and a post-BD FEV1/FVC ratio < 0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (n = 215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC exposure, first post-9/11 FEV1/FVC ratio, and BMI included as covariates. RESULTS: BD-PFT diagnosed asthma/COPD overlap in 99 subjects (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration ≥ 300 cells/µL was associated with increased risk of asthma/COPD overlap (hazard ratio [HR], 1.85; 95% CI, 1.16-2.95) but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR, 1.51 per doubling of cytokine concentration; 95% CI, 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HRs of 1.73 [95% CI, 1.27-2.35] and 2.06 [95% CI, 1.31-3.23], respectively). CONCLUSIONS: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.

Blood Eosinophils and World Trade Center Exposure Predict Surgery in Chronic Rhinosinusitis. A 13.5-Year Longitudinal Study.

RATIONALE: The World Trade Center (WTC) collapse generated caustic airborne particulates that caused chronic rhinosinusitis in exposed Fire Department of New York firefighters. Surgery was performed when symptoms remained uncontrolled despite medical management. OBJECTIVES: To identify predictors of surgical intervention for chronic rhinosinusitis in firefighters exposed to airborne irritants at the WTC collapse site. METHODS: We assessed in 8,227 firefighters with WTC exposure between September 11, 2001 (9/11), and September 25, 2001, including WTC-site arrival time, months of rescue and recovery work, and eosinophil concentration measured between 9/11 and March 10, 2003. We assessed the association of serum cytokines and immunoglobulins with eosinophil concentration and surgery for rhinosinusitis in 112 surgical cases and 376 control subjects with serum available from the first 6 months after exposure to the WTC collapse site. MEASUREMENTS AND MAIN RESULTS: Between 9/11 and March 10, 2015, the surgery rate was 0.47 cases per 100 person-years. In the first 18 months post-9/11, surgical patients had higher mean blood eosinophil levels than study cohort patients (219 ± 155 vs. 191 ± 134; P < 0.0001). Increased surgery risk was associated with increasing blood eosinophil counts (hazard ratio [HR], 1.12 per 100 cells/µl; 95% confidence interval [CI], 1.07-1.17; P < 0.001); arriving at the WTC site on 9/11 or September 12, 2001 (HR, 1.43; 95% CI, 1.04-1.99; P = 0.03); and working 6 months or longer at the WTC site (HR, 1.48; 95% CI, 1.14-1.93; P < 0.01). Median blood eosinophil levels for surgical patients were above levels for the cohort in all 18-month intervals March 11, 2000, through March 10, 2015, using 51,163 measurements representing 97,733 person-years of observation. Increasing age, increasing IL-17A, and low IgA in serum from 2001 to 2002 predicted blood eosinophil concentration in surgical patients but not in control subjects (R(2) = 0.26, P < 0.0001; vs. R(2) = 0.008, P = 0.56). CONCLUSIONS: Increasing blood eosinophil concentration predicts surgical intervention for chronic rhinosinusitis, particularly in those with intense acute and prolonged exposure to airborne irritants. WTC-exposed Fire Department of New York firefighters who underwent irritant-associated sinus surgery are immunologically different from the cohort. Surgical patients have a higher blood eosinophil levels that is associated with mediators of mucosal immunity.