Use Of Inhaled Corticosteroids Research Articles

Risk Factors and Prognosis of Nontuberculous Mycobacteria Infection in a High Prevalence of Tuberculosis Setting

Background: The prevalence and incidence of Non­tuberculous Mycobacteria (NTM) infections in the world in general have continued to in­cre­ase in the last two to three decades. Until now i­den­tification and testing of NTM sensitivity in Indonesia is still very difficult to do in daily health services. Thus, NTM infection is still a ne­glected case and misdiagnosis often occurs. In these conditions, one of the things that is very im­portant to help clinicians in the management of NTM infections is information about patient characteristics and how the relationship of risk factors for NTM infection with prognosis. Subjects and Method: The study was con­duc­ted retrospectively using data on the medical re­cords of patients with positive culture of NTM at the Surakarta Center for Community Lung Health (BBKPM) for 3 years (2016-2018). A total of 134 samples were selected for this study with total sampling. The dependent variable is the prognosis of infection. The independent variables were gender, age, occupation, history of inhaled corticosteroid use, antibiotic therapy, and under­lying disease. Data were analyzed using multiple logistic regression. Results: The number of samples is 143 medical records. Most of the patients in this study were male (62.90%) and aged less than 60 years (79.70%). The majority of patients work not as far­mers (80.40%). Most patients had no history of inhaled corticosteroid use (89.50%). The­ra­pe­utic factors indicate that the majority of patients receive combined antibiotic therapy (68.5%). As many as 42% of patients with NTM infection have an underlying disease. Underlying disease in patients is mostly in the form of diabetes me­l­litus (DM) in 13.3% and in the former tuber­cu­losis in 4.9%. Based on the Chi-Square test, a sig­nificant relationship was found between the­ra­peutic factors, history of inhaled corti­cos­teroid use, and type of work, and the patient's prog­no­sis. Based on mult­ivariable testing, the factor of antibiotic therapy is the most influential variable on a pa­tient's prognosis. Conclusion: Risk factors related to the patient's prog­nosis are occupation, use of inhaled cor­tico­steroids and antibiotic therapy. Keywords: Nontuberculous Mycobacteria, risk factors, prognosis, Center for Community Lung Health Correspondence: Leli Saptawati. Department of Microbiology, Fa­culty of Medicine, Universitas Sebelas Maret, In­do­nesia. Jl. Ir. Soetami no. 36A Kentingan Su­ra­karta, Indonesia. Email: llsapt_md@yahoo.­co.­id. Mobile: (0271) 632489. Journal of Epidemiology and Public Health (2020), 5(1): 79-87 https://doi.org/10.26911/jepublichealth.2020.05.01.08

Distance Education to Improve the Quality of Asthma Treatment in Primary Health Care

Objective: The mere dissemination of standard care recommendations has been insufficient to improve clinical results in patients with asthma. The objective of the present study was to evaluate the clinical effectiveness of a multifaceted asthma distance education for primary care providers. Methods: Cluster randomized controlled trial. Full primary care teams were included if they had access to telehealth support and free basic asthma treatment. Before randomization, selected teams indicated asthma patients between 5-45 years old for inclusion. The intervention group received three interactive online sessions, printed educational material, reminders, booklet for patients, and frequent stimulus to use consulting services. The control group received no intervention. Symptomfree days per two weeks was the primary result. Controlled asthma, unscheduled asthma doctor visits, and preventive inhaled corticosteroid use were the secondary results. Six months after intervention, the results were compared with baseline data using generalized estimating equations for repeated measures and clustering effect. Results: Were enrolled 71 primary care teams and 443 individuals. Most patients (60.3%) were female, and 44% were younger than 12 years old. The attendance of interactive sessions by the teams was 50%. The odds ratio (OR) for additional symptom-free day was 1.31 (95%CI 0.61-2.82; p=0.49). For the secondary results, the results were: controlled asthma OR 1.29 (95%CI 0.89-1.87; p=0.18); unscheduled asthma doctor visits OR 0.81 (95%CI 0.60-1.10; p=0.17); and preventive inhaled corticosteroid use OR 1.02 (95%CI 0.71-1.47; p=0.91). Conclusions: Multifaceted distance education in asthma care for primary care providers was not effective to improve patients’ results. Telemedicine needs to deal with significant obstacles in professional education. ClinicalTrials.gov registry: NCT01595971.

Efficacy of House Dust Mite Sublingual Tablet in the Treatment of Allergic Rhinoconjunctivitis: A Randomized Trial in a Pediatric Population

To investigate the efficacy, safety, and immunologic response of standardized sublingual house dust mite (HDM) tablets in Japanese pediatric patients.Included in the study were patients ≥5 and ≤16 years of age with allergic rhinitis symptoms for ≥2 years, a score of ≥3 on quantitative analysis of specific immunoglobulin E antibody to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae antigens, positive nasal provocation test result for HDM, and Rhinitis Total Symptom Score ≥6 points per day for 7 days before randomization. Those with symptoms from other allergens, mild persistent or more-severe asthma, or inhaled corticosteroid use were excluded.This multicenter, double-blind, randomized placebo-controlled trial was conducted at 51 Japanese medical institutions from October 2015 to December 2016. Subjects were randomly assigned 1:1 to placebo or HDM tablets with an index of reactivity of 300 daily for 52 weeks. Symptoms and rescue medication use were recorded daily in a patient diary. The primary end point was the average adjusted symptom score for week 48 to 52, derived from daily Rhinitis Total Symptom Scores and adjusted for rescue medication use.Of 438 patients who were randomly assigned, 193 patients in the treatment group and 210 patients in the placebo group completed the study. The average adjusted symptom score was significantly lower in the treatment group compared with placebo (6.32 vs 7.27, P = .0005), with a least-squares mean difference of −13.1%. Improvement was seen at weeks 8 to 10 and was maintained throughout. Nasal Individual Symptom Scores were significantly lower in the treatment group, whereas Average Rescue Medication Scores and Ocular Individual Symptom Scores were not. Specific immunoglobulin E antibodies to HDM nearly doubled, whereas specific immunoglobulin G4 antibodies approximately tripled in the treatment group. Mild or moderate adverse events (oral pruritus, mouth edema, throat irritation, ear pruritus, and mouth swelling) occurred in most patients (96.8% of treated patients, 94.5% of placebo patients), typically from days 1 to 14. Two serious adverse events were reported in the placebo group and 6 were reported in the treatment group, leading to drug discontinuation in 1 patient with pseudocroup. Overall, 8% of randomly assigned patients discontinued the study, mostly because of adverse effects. There were no deaths or anaphylactic events requiring intramuscular epinephrine.This study demonstrates efficacy and safety of HDM sublingual tablets in pediatric patients with perennial allergic rhinitis due to HDM allergy. Treatment conferred significant and sustained improvement in symptom scores, with a similar immunologic response and safety profile, as previously shown in older age groups.This study is limited by a lack of objective outcomes, such as peak nasal inspiratory flow or nasal provocation tests. The investigators also excluded patients with persistent asthma and symptomatic rhinitis due to other allergens, which commonly occur in patients with HDM-triggered rhinitis. Although modest improvement in symptoms was shown, daily therapy over a 52-week treatment course may be impractical for pediatric patients. One likely goal of HDM immunotherapy may be to decrease use of other medications, but this was not seen in the current study. Further studies are needed in this population to assess optimal treatment duration and whether treatment confers sustained benefit after drug discontinuation.

Inhaled corticosteroid use and the incidence of lung cancer in COPD.

Inhaled corticosteroids (ICS) are suggested for potential chemoprevention of lung cancer. Several observational studies in patients with chronic obstructive pulmonary disease (COPD) reported inconsistent results, either significant reductions in lung cancer incidence with ICS use or no effect. We assessed this association, using an approach that avoided biases affecting some of the studies. A cohort of patients with COPD, new users of long-acting bronchodilators over 2000-2014, was formed using the Quebec healthcare databases, and followed until 2015 for a first diagnosis of lung cancer. A 1-year delay after cohort entry was used to avoid protopathic bias and a 1-year latency period was included after the initiation of ICS use. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) of lung cancer associated with ICS exposure, adjusted for covariates. The cohort involved 63 276 subjects, including 63% receiving ICS, with 3743 lung cancers occurring during a mean follow-up of 5 years. The adjusted HR of lung cancer associated with any ICS exposure was 1.01 (95% CI 0.94-1.08), relative to no ICS use. The HR with longer time (>4 years) since ICS initiation was 0.92 (95% CI 0.83-1.03), while with higher mean daily ICS dose (>1000 μg fluticasone equivalents) was 1.36 (95% CI 1.03-1.81). Inhaled corticosteroid use is not associated with a reduction in lung cancer incidence in patients with COPD. Observational studies reporting such reduction may have been affected by time-related biases and the inclusion of patients with asthma. The proposition of a randomised trial warrants some caution.

Management of Australian Adults with Bronchiectasis in Tertiary Care: Evidence-Based or Access-Driven?

Australian data regarding the management of patients with bronchiectasis is scarce. We sought to compare the management of adults with bronchiectasis attending tertiary Australian centres with recent national and international guidelines. The Australian Bronchiectasis Registry is a centralised database of patients with radiologically confirmed bronchiectasis unrelated to cystic fibrosis recruited from 14 tertiary Australian hospitals. We excluded children (<18years) and those with incomplete data, leaving 589 adults for cross-sectional analyses. We compared the proportion of patients receiving certain therapies, as compared to the proportion eligible for those treatments according to the current guidelines and baseline clinical information available from the registry. Pulmonary rehabilitation was attended by 22%, although it was indicated in 67% of the cohort. Airway clearance was undertaken in 52% of patients, although 71% reported chronic productive cough. Sputum bacterial culture results were available for 59%, and mycobacterial culture results were available for 29% of the cohort. Inhaled antibiotics were used in half of potentially eligible patients. Despite guideline recommendations against routine use, inhaled corticosteroids were used in 48% of patients. Long-term macrolides were used in 28% of participants. Discrepancies exist between guideline recommendations and real-world treatment of bronchiectasis in Australia, even in tertiary centres. These findings suggest the need for increased patient referral to pulmonary rehabilitation, increased attention to airway clearance, increased collection of sputum samples (especially for mycobacterial culture) and rationalisation of inhaled corticosteroid use. These findings encourage a review of treatment access and will inform ongoing education to promote evidence-based care for people living with bronchiectasis.

Hair cortisol and inhaled corticosteroid use in asthmatic children.

BackgroundAdrenal suppression is a side effect of long‐term use of inhaled corticosteroids (ICS). Hair cortisol concentration (HCC) measurement is a noninvasive tool for measuring adrenal function that may be useful for asthmatic patients who are on long‐term ICS treatment. The aim of this study was to compare HCC between children with and without asthma and to explore the association between HCC and ICS dose in asthmatic children.MethodsA cross‐sectional observational study in subjects with or without asthma (n = 72 and 226, respectively, age 6‐21 years). Hair samples were obtained from the posterior vertex for each subject and data on medication use were collected using questionnaires. HCC was analyzed by liquid chromatography‐mass spectrometry in the most proximal 3 cm of hair.ResultsMedian HCC was significantly lower in subjects with asthma than in subjects without asthma: 1.83 pg/mg and 2.39 pg/mg, respectively (P value after adjustment for age, sex, and body mass index: .036). Median HCC was 1.98 pg/mg in asthmatics using no ICS, 1.84 pg/mg in those using a low dose, 1.75 pg/mg in those on a medium dose, and 1.46 in those using a high ICS dose (P = .54).ConclusionWe observed a significantly lower HCC in asthmatics than in healthy controls and a nonsignificant trend of lower HCC with increasing ICS dose. Whether HCC measurement may be used to detect individuals at risk for hypocortisolism and may be useful to monitor adrenal function in asthmatic children using ICS needs to be further investigated.

2221. Chlamydia pneumoniae (Cpn) Induces IFN-γ Responses in Peripheral Blood Mononuclear Cells (PBMC) from Pediatric and Adult Asthma Patients: Effects of Age and Inhaled Corticosteroid Use

BackgroundChlamydia pneumoniae (Cpn) is unique in its ability to cause chronic infections, potentially triggering asthma exacerbations as well as subsequent asthma development. Th1-mediated immunity and IFN-γ are critical for clearing chlamydial infections. Persistent or recent Cpn infection may be identified in vitro by detecting T-helper cytokine IFN-γ produced by peripheral blood mononuclear cells (PBMC) stimulated by Cpn. Inhaled corticosteroids (ICS) may have an inhibitory effect on IFN-γ. Prior studies have shown increased Th2 responses upon in vitro Cpn stimulation with increased age. Our aim was to determine whether age and inhaled corticosteroid (ICS) use affect Cpn-induced PBMC produced IFN-γ levels.MethodsPediatric and adult subjects with (n = 23) and without (n = 10) asthma were enrolled. PBMC obtained from all subjects were stimulated with Cpn (MOI = 0.1 x48h) in vitro. IFN-γ levels in culture supernatants were determined by ELISA and reported as pg/mL. Nasopharyngeal (NP) swabs were tested for Cpn using Real-Time PCR. Statistical analysis for continuous variables was performed using the Mann–Whitney U test.ResultsNone of the subjects were positive for Cpn by PCR on NP swab. Levels of IFN-γ produced by PBMC stimulated by Cpn were similar between asthmatic vs. control subjects (41.7 vs. 68.8, respectively; P = 0.72) and between pediatric and adult subjects with asthma (IFN-γ 54 vs. 20.1 respectively, P = 0.95). Pediatric subjects with asthma who received ICS had lower IFN-γ levels than those who did not (median IFN-γ 25.5 vs. 209; P = 0.003).ConclusionOur finding of lower IFN-γ levels among asthma patients on ICS compared with those not on ICS suggests that ICS use may dampen the systemic inflammatory response. While we did not find a statistically significant difference between pediatric and adult age groups in this pilot study, there was a trend to higher Cpn-induced IFN-γ levels among younger pediatric subjects. Future prospective studies should further define predictors of diminished IFN-γ responses in patients with asthma.Disclosures All authors: No reported disclosures.

COPD EXACERBATION RATE BY BASELINE COPD ASSESSMENT TEST SCORE IN THE DYNAGITO STUDY

COPD EXACERBATION RATE BY BASELINE COPD ASSESSMENT TEST SCORE IN THE DYNAGITO STUDY

Efficacy and Safety of HDM SLIT Tablet in Japanese Adults with Allergic Asthma

The standardized quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT) tablet has demonstrated efficacy and safety for allergic asthma (AA) in European trials. To evaluate the efficacy and safety of SQ HDM SLIT tablet treatment for up to 19 months in Japanese adults with AA. In this randomized, double-blind, placebo-controlled trial, patients aged 18 to 64 years with AA were randomly assigned (1:1:1) to SQ HDM SLIT doses of 10,000 or 20,000 Japanese Allergy Unit or placebo. Subjects had Asthma Control Questionnaire score of 1.0 to 1.5 and daily inhaled corticosteroid use of 200 to 400 μg of fluticasone propionate at randomization. The primary end point was the time from randomization to the first asthma exacerbation as the inhaled corticosteroid dose was being reduced. Of the 826 randomized subjects, 693 (84%) completed the trial. No statistically significant differences between the active groups and the placebo group were observed for the primary or any other efficacy end points. However, post hoc analysis indicated a significant difference between the 20,000 Japanese Allergy Unit and placebo groups among subjects who used a short-acting β2-agonist during the baseline period (hazard ratio, 0.70; 95% CI, 0.48-1.00; P= .04997). No deaths or anaphylactic reactions were reported. Most adverse events were mild to moderate in severity. The trial demonstrated a favorable safety profile of the SQ HDM SLIT tablet in Japanese adult patients with AA. The treatment appeared to be efficacious in patients requiring rescue medication (ie, short-acting β2-agonist) at baseline in the efficacy assessment using asthma exacerbation during inhaled corticosteroid reduction (JapicCTI number 121847).

Inhaled corticosteroid use during pregnancy among women with asthma: A systematic review and meta-analysis.

Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users. We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N=45; Aim 2, N=13; and Aim 3, N=5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%); 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%). The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.

Economic Impact of Reducing Inappropriate Inhaled Corticosteroids Use in Patients With Chronic Obstructive Pulmonary Disease: ISPOR's Guidance on Budget Impact in Practice

ObjectivesTo assess the budget impact of restricting inappropriate inhaled corticosteroids (ICS) use according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)-guidelines indication for ICS use in the chronic obstructive pulmonary disease (COPD)-population, taking The Netherlands as a reference case. MethodsA budget impact model was developed and closely aligned with the International Society for Pharmacoeconomics and Outcomes Research best-practice guidelines. The model estimates the impact of pharmacologic COPD maintenance treatments on clinical events (exacerbations and pneumonias) and associated healthcare utilization and costs. The current treatment mix included all maintenance treatments including long-acting muscarinic antagonists (LAMA), long-acting β2-agonists (LABA), LABA/ICS, LABA/LAMA, and triple therapy (LABA/LAMA/ICS). We modeled a situation where 25% of patients would use ICS-containing treatments and compared this to the current Dutch situation with 60% ICS use. A 5-year time horizon with a Dutch healthcare payer's perspective was used. In sensitivity analyses, a range of values for absolute ICS reduction (20%-40%), relative risks of exacerbations and pneumonia events, and other input parameters were explored. ResultsOver a period of 5 years, the new treatment mix with Global Initiative for Chronic Obstructive Lung Disease guideline recommended ICS, and LABA/LAMA use resulted in potential avoidance of 17 405 exacerbations and 11 984 pneumonias and accompanied savings of €84 million in the base-case scenario. Savings were consistent in various sensitivity analyses, indicating cost savings between €30 and €200 million. ConclusionReducing inappropriate ICS use and increasing use of LABA/LAMA in COPD patients could result in a reduction of exacerbations and pneumonias, corresponding with a reduction in total costs for COPD in The Netherlands.

Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis

Bronchiectasis guidelines recommend long-term macrolide treatment for patients with three or more exacerbations per year without Pseudomonas aeruginosa infection. Randomised controlled trials suggest that long-term macrolide treatment can prevent exacerbations in adult patients with bronchiectasis, but these individual studies have been too small to do meaningful subgroup analyses. We did a systematic review and individual patient data (IPD) meta-analysis to explore macrolide benefit in subpopulations, including those in which macrolide therapy is not currently recommended. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science from Jan 1, 2000, to Sept 30, 2018, to identify double blind, randomised, placebo-controlled trials of macrolide antibiotics in adult patients with bronchiectasis. We applied no language restrictions. Randomised controlled trials were eligible if treatment was defined a priori as long term and had a primary or secondary outcome of bronchiectasis exacerbations. Studies in patients with cystic fibrosis bronchiectasis were excluded. The primary outcome of the meta-analysis was frequency of exacerbations requiring treatment with antibiotics. Secondary endpoints were time to first exacerbation, change in quality of life according to the St George's Respiratory Questionnaire (SGRQ), and change in FEV1. IPD meta-analysis was done using fixed effects models adjusting for age, sex, FEV1, and trial. We did prespecified subgroup analyses for each of the primary and secondary endpoints using one-step meta-analysis only. Subgroups were defined by age, sex, previous exacerbation frequency, smoking status, inhaled corticosteroid use at baseline, body-mass index at baseline, cause, C-reactive protein at baseline, baseline FEV1 percentage of predicted, SGRQ total score, and Pseudomonas aeruginosa in sputum culture at baseline. The meta-analysis is registered with the PROSPERO international register of systematic reviews, number CRD42018102908. Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio [IRR] 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV1 (67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains. Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics. This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful. However, downsides of long-term macrolide treatment must also be taken into account. European Respiratory Society.

A Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma

Symptom-based adjustment (SBA) of inhaled corticosteroids may be an alternative patient-centered approach in which day-to-day inhaled corticosteroid use is adjusted by symptoms and short-acting β-agonist need. To evaluate the effectiveness of SBA in the primary care setting. We conducted a randomized, open-label, pragmatic equivalence trial in African-American children (6-17 years old) with mild asthma managed by 12 primary care providers (PCPs). A total of 206 participants were randomized to SBA (as-needed beclomethasone 80 μg with rescue short-acting β-agonist) or provider-based guideline-directed adjustment (PBA): maintenance beclomethasone 80 μg/d (6-11 years old), 160 μg/d (12-17 years old), with subsequent guideline-based dose adjustment by PCPs. PCPs implemented both treatment assignments, with outcomes measured by blinded staff. All participants received symptom recognition and albuterol use education from peer educators. Primary outcome was change in asthma control (measured by Asthma Control Test [ACT]/childhood ACT [cACT]) over 12 months. Participants had adequately controlled asthma (mean ACT or cACT score= 21.6 ± 2.8) at baseline. After 1 year, there was no significant between-group difference in change in ACT scores (SBA- PBA): ACT: -0.88 (95% CI,-2.19 to 0.42), cACT:-0.73 (-2.09 to 0.62), or combined ACT and cACT (P= .10), and was within the predefined statistical clinical equivalence. The proportion with an exacerbation and measures of lung function were similar between groups. Compared with PBA, SBA led to less beclomethasone use (SBA: 526 μg/mo [95% CI, 412-639 μg] vs PBA: 1961 μg/mo [95% CI, 1681-2241]; P < .0001). More parents in the SBA arm felt they were managing their child's asthma. SBA in African-American children with mild asthma was similar to PBA in asthma control and events when implemented by PCPs with lower inhaled corticosteroid exposure.

Racial/Ethnic-Specific Differences in the Effects of Inhaled Corticosteroid Use on Bronchodilator Response in Patients With Asthma.

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P=0.028) but not African Americans (0.49%, P=0.426) or Puerto Ricans (0.16%, P=0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response.

Novel clinical scores for occupational asthma due to exposure to high-molecular-weight agents

ObjectiveSpecific inhalation challenge (SIC) as the reference diagnostic test for occupational asthma (OA) is not widely available worldwide. We aimed to develop non-SIC-based models for OA.MethodsOf 427 workers who were...

Chronic obstructive pulmonary disease upper airway microbiota alpha diversity is associated with exacerbation phenotype: a case-control observational study

BackgroundChronic obstructive pulmonary disease (COPD) frequent exacerbators (FE) suffer increased morbidity and mortality compared to infrequent exacerbators (IE). The association between the oral and sputum microbiota and exacerbation phenotype is not well defined. The objective of this study was to determine key features that differentiate the oral and sputum microbiota of FEs from the microbiota of IEs during periods of clinical stability.MethodsWe recruited 11 FE and 11 IE who had not used antibiotics or systemic corticosteroids in the last 1 month. Subjects provided oral wash and sputum samples, which underwent 16S V4 MiSeq sequencing and qPCR of 16S rRNA. Data were analyzed using Dada2 and R.ResultsFE and IE were similar in terms of age, FEV1 percent predicted (FEV1pp), pack-years of tobacco exposure, and St. George’s Respiratory Questionnaire score. 16S copy numbers were significantly greater in sputum vs. oral wash (p = 0.01), but phenotype was not associated with copy number. Shannon diversity was significantly greater in oral samples compared to sputum (p = 0.001), and IE samples were more diverse than FE samples (p < 0.001). Sputum samples from FE had more Haemophilus and Moraxella compared to IE sputum samples, due to dominance of these COPD-associated taxa in three FE sputum samples. Amplicon sequencing variant (ASV)-level analysis of sputum samples revealed one ASV (Actinomyces) was significantly more abundant in IE vs. FE sputum (padj = 0.048, Wilcoxon rank-sum test), and this persisted after controlling for FEV1pp. Principal coordinate analysis using Bray-Curtis distance with PERMANOVA analyses demonstrated clustering by anatomic site, phenotype, inhaled corticosteroid use, current tobacco use, COPD severity, and last professional dental cleaning.ConclusionsFE have less diverse oral and sputum microbiota than IE. Actinomyces was significantly more abundant in IE sputum than FE sputum. The oral and sputum microbiota of COPD subjects cluster based on multiple clinical factors, including exacerbation phenotype. Even during periods of clinical stability, the frequent exacerbator phenotype is associated with decreased alpha diversity, beta-diversity clustering, and changes in taxonomic abundance.

As-Needed Combination Budesonide/Formoterol for Intermittent and Mild Asthma?

As-needed use of combination inhaled corticosteroids (ICS) and fast-acting, long-acting β-agonists (LABAs) prevent asthma exacerbations as effectively

Validity of the diagnosis of pneumonia in hospitalised patients with COPD.

RationaleExacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia are two of the most common reasons for acute hospital admissions. Acute exacerbations and pneumonia present with similar symptoms in COPD patients, representing a diagnostic challenge with a significant impact on patient outcomes. The objectives of this study were to compare the prevalence of radiographic consolidation with the discharge diagnoses of hospitalised COPD patients.MethodsCOPD patients admitted to three UK hospitals over a 3-year period were identified. Participants were included if they were admitted with an acute respiratory illness, COPD was confirmed by spirometry and a chest radiograph was performed within 24 h of admission. Pneumonia was defined as consolidation on chest radiograph reviewed by two independent observersResultsThere were 941 admissions in 621 patients included in the final analysis. In 235 admissions, consolidation was present on chest radiography and there were 706 admissions without consolidation. Of the 235 admissions with consolidation, only 42.9% had a discharge diagnosis of pneumonia; 90.7% of patients without consolidation had a discharge diagnosis of COPD exacerbation. The presence of consolidation was associated with increased rate of high-dependency care admission, increased mortality and prolonged length of stay. Inhaled corticosteroid use was associated with recurrent pneumonia.ConclusionsPneumonia is underdiagnosed in patients with COPD. Radiographic consolidation is associated with worse outcomes and prolonged length of stay. Incorrect diagnosis could result in inappropriate use of inhaled corticosteroids. Future guidelines should specifically address the diagnosis and management of pneumonia in COPD.

Inhaled corticosteroid use by exacerbations and eosinophils: a real-world COPD population.

Background: Blood eosinophils may predict response to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) where ICS is recommended in patients at high risk of exacerbations. The proportion of patients who may benefit the most from ICS-based therapy was quantified in a real-world population.Materials and methods: European data from the Adelphi Real World Respiratory Disease Specific Programme™ 2017 survey were collected from consecutive COPD patients by participating physicians. Overall, 1,528 patients were assessable for Global Initiative for COPD (GOLD) 2017 status and were included in the analysis.Results: More GOLD D patients had elevated eosinophil counts compared with GOLD B. The proportions of GOLD D patients with a history of ≥2 exacerbations and eosinophil counts of ≥150, ≥300, and ≥400 cells/µL were 81.2%, 39.4%, and 24.6%, respectively. In total, 10.6% of the patients had ≥300 eosinophils/µL and a history of ≥2 exacerbations. ICS-based therapy was received by 41.5% of GOLD B and 68.0% of GOLD D patients.Conclusion: There was no apparent relation between ICS use and eosinophil blood count. There are differences in the distributions of patients with frequent exacerbations and/or high blood eosinophil counts and the use of ICS in COPD. These data may provide information for the implementation of future treatment recommendations.

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

ObjectivesWe aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. DesignData were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and ParticipantsOlder hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. MeasuresWe evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence. ResultsAt hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (≥5 drugs) at admission [odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81], a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90). Conclusions/ImplicationsCOPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events.