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The disease origins of idiopathic pulmonary fibrosis (IPF), which occurs at higher rates in certain races/ethnicities, are not understood. The highest rates occur in white persons of European descent, particularly those with light skin, who are also susceptible to lysosomal organelle dysfunction of the skin leading to fibroproliferative disease . We had observed clinically that the vast majority of patients with IPF had light-colored eyes, suggesting a phenotypic characteristic.We pursued this observation through a research database from the USA Veterans Administration, a population that has a high occurrence of IPF due to predominance of elderly male smokers. Using this medical records database, which included facial photos, we compared the frequency of light (blue, green, hazel) and dark (light brown, brown) eyes among white patients diagnosed with IPF compared with a control group of lung granuloma only (no other radiologic evidence of interstitial lung disease).Light eye color was significantly more prevalent in patients with IPF than in the control group with lung granuloma [114/147 (77.6%) versus 129/263 (49.0%], p 0.001), indicating that light-colored eyes are a phenotype associated with IPF .We provide evidence that light eye color is predominant among white persons with IPF.

Data collected through ongoing, state-based, cross-sectional health surveys could be used to better understand the contribution of respiratory symptoms to impaired health among the US adult population.We used the 2015 Behavioral Risk Factor Surveillance System telephone health survey in four states (Kentucky, Florida, South Carolina, Texas) to describe the relationship between symptoms, associated factors such as tobacco smoking, and health impairments. Self-reported productive cough, shortness of breath (SOB), and dyspnea on exertion (DOE) were categorized as minimal, moderate, or severe. Data were analyzed using multiple logistic regression models with age as a covariate to assess relationships of symptoms with other factors.Among adults ≥ 18 years, respiratory impairment [current asthma, chronic obstructive pulmonary disease (COPD), or a current moderate or severe symptom] occurred in 39.1% of the population. More than half of adults reporting moderate or severe symptoms had not been diagnosed with asthma or COPD, particularly with DOE and productive cough. Subjects were at greater risk of moderate and severe SOB or productive cough with increasing age, prolonged smoking duration (≥ 20 years), being an ever-smoker, or if reporting COPD, current asthma, or any other comorbidity except cancer. Morbid obesity [body mass index (BMI) 35 kg/mIn the largest US survey in decades, we provide a current perspective of respiratory symptoms among adults of all ages. While known risk factors were apparent, low-risk persons also frequently reported symptoms and impairments.

Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)—a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)—are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.

Modernizing inhaled medications through digital technology can help address persistent problems of non-adherence and poor inhaler technique in patients with obstructive lung diseases. With a growing body of supportive clinical studies, advances in digital inhaler sensors and platforms, greater support from payers and healthcare organizations, significant growth with these technologies is expected. While all digital (smart) inhalers record adherence, these are distinguished by their compatibility with commercial inhalers, capabilities to guide inhaler technique, use of patient-reported outcomes, and user-friendliness for both the healthcare professional (HCP) and patient. Due to the complexity and novelty of employing digital inhalers, collaboration with multiple entities within health systems is necessary and a well-planned integration is needed. For HCPs and patients, cybersecurity and privacy are critical, it will require review by each healthcare organization. In the US, some payers reimburse for remote monitoring using digital inhalers, but reimbursement is currently unavailable in other countries. There are several models for remote patient care, as employing an active, ongoing digital interface between the HCP and patient or they may choose to only review data at clinical encounters. Personalization of therapies and feedback are key to success. While digital inhaler malfunction uncommonly occurs, patient attrition over a year is significant. Some patients will be challenged to use digital platforms or have the necessary technology. Additional research is needed to address cost-effectiveness, in vivo accuracy of inspiratory measurement capable devices, ability to teach inhaler technique, their application for monitoring lung function, and lastly real-world adoption and implementation in routine clinical practice.

This study aimed to identify if individuals with mild to severe alpha-1 antitrypsin deficiency (AATD) are at higher risk for developing obstructive sleep apnea (OSA) than the general population. A seven-question sleep apnea risk assessment questionnaire, STOP-BAG, was applied to 2338 participant responses from the Alpha-1 Coded Testing Study (ACT) and 4638 participant responses from the Kentucky Behavioral Risk Factor Survey (KyBRFS). Propensity scores were generated from a logistic regression model using continuous variables of age and body mass index (BMI). STOP-BAG scores were analyzed using chi-square analysis on this matched cohort to assess OSA risk in AATD. Self-reported OSA was higher in the KyBRFS cohort (14.5%) than in individuals with mild or severe AATD (11.2%) (p = 0.012). However, a higher percentage of the AATD cohort met clinically meaningful thresholds for STOP-BAG scores ≥ 5 (22.7%) than the KyBRFS cohort (13.0%) (p = 0.001). These differences persisted despite 1:1 propensity score matching on age and BMI to account for differences in baseline characteristics. No statistically significant difference in OSA risk between AATD genotypes was found. AATD appears to have higher risk for OSA than the general population. The 11.2% prevalence of diagnosed OSA in the AATD population is much lower than symptom scores would predict. Further studies are needed to validate the possibility that elastin loss is involved in OSA pathogenesis.

Background Bronchiectasis is characterized by recurrent infectious exacerbations. No existing data inform preventive strategy for exacerbations beyond chronic macrolides. OM-85 BV, an immunostimulant, has been shown to prevent recurrent respiratory infections. We initiated this 1-year, multi-centered, double-blind, and controlled trial to investigate the PReventive effect of OM-85 BV on Bronchiectasis Exacerbations in Chinese patients (iPROBE). Methods Patients with bronchiectasis aged 18 to 75 years, having at least one exacerbation in the past year, were randomized to receive, in addition to any respiratory medications, two courses of 7 mg of OM-85 BV or matching placebo (one capsule orally per day for 10 days a month) for 3 consecutive months, followed by 3 months without treatment. The primary outcomes included the number of acute infectious exacerbations and the time to first exacerbation. Secondary endpoints included patient-reported respiratory outcomes. Safety measures were also assessed. Results Among the 196 participants, 99 were in the OM-85 BV group and 97 in the placebo group. At week 52, the mean number of acute exacerbations per patient was equal to 0.98 and 0.75, respectively, in the two groups (P=0.14). Difference in the time to first pulmonary exacerbation was not statistically significant (P=0.11). There was no statistically significant difference in any secondary end-points. The safety profile in the two arms was good and the majority of adverse events were mild. Conclusions OM-85 BV did not demonstrate protection in decreasing pulmonary exacerbations of bronchiectasis in this trial performed in Chinese patients. It had good safety profile.

The 2020 Global Initiative for Obstructive Lung Disease (GOLD) Report highlights the importance of sputum purulence in the decision to prescribe antibiotics for acute exacerbations. The purpose of this systematic review and meta-analysis was to evaluate the strength of literature supporting inclusion of sputum purulence in criteria utilized to evaluate if antimicrobials are indicated in acute COPD exacerbation. A total of 6 observational studies met inclusion criteria for this meta-analysis. Sputum purulence was defined by visual assessment of color, either subjectively by providers and/or patients or by a colored chart, where green or yellow sputum was considered purulent. Four of the studies were primarily conducted in hospitalized patients, one in the emergency department, and one in the primary care setting. Five studies relied upon expectorated sputum and one used bronchoscopy to obtain sputum samples for bacterial cultures. Compared with mucoid sputum, purulent sputum had a significantly higher probability of positive bacterial culture results (RR = 2.14, 95%CI [1.25, 3.67]

Impressive advances in inhalation therapy for patients with asthma and chronic obstructive pulmonary disease (COPD) have occurred in recent years. However, important gaps in care remain, particularly relating to poor adherence to inhaled therapies. Digital inhaler health platforms which incorporate digital inhalers to monitor time and date of dosing are an effective disease and medication management tool, promoting collaborative care between clinicians and patients, and providing more in-depth understanding of actual inhaler use. With advances in technology, nearly all inhalers can be digitalized with add-on or embedded sensors to record and transmit data quantitating inhaler actuations, and some have additional capabilities to evaluate inhaler technique. In addition to providing an objective and readily available measure of adherence, they allow patients to interact with the device directly or through their self-management smartphone application such as via alerts and recording of health status. Clinicians can access these data remotely and during patient encounters, to better inform them about disease status and medication adherence and inhaler technique. The ability for remote patient monitoring is accelerating interest in and the use of these devices in clinical practice and research settings. More than 20 clinical studies of digital inhalers in asthma or COPD collectively show improvement in medication adherence, exacerbation risk, and patient outcomes with digital inhalers. These studies support previous findings about patient inhaler use and behaviors, but with greater granularity, and reveal some new findings about patient medication-taking behaviors. Digital devices that record inspiratory flows with inhaler use can guide proper inhaler technique and may prove to be a clinically useful lung function measure. Adoption of digital inhalers into practice is still early, and additional research is needed to determine patient and clinician acceptability, the appropriate place of these devices in the therapeutic regimen, and their cost effectiveness. Video: Digital Inhalers for Asthma or Chronic Obstructive Pulmonary Disease: A Scientific Perspective (MP4 74535 kb) Supplementary Information The online version supplementary material available at 10.1007/s41030-021-00167-4.

Purpose Adequate peak inspiratory flow rate (PIFR) is required for drug dispersion with dry powder inhalers (DPIs). Prevalence of PIFR discordance (suboptimal PIFR with prescribed inhalers) and factors influencing device-specific PIFR are unclear in COPD. The objective of this study was to determine the prevalence of PIFR discordance and associated clinical factors in a stable COPD population. Patients and methods An observational, single-center, cohort study was conducted including 66 outpatients with COPD. PIFR was measured using the In-Check™ Dial with applied resistance of prescribed inhalers. Participants were defined as discordant if measured PIFR was

STUDY OBJECTIVES: Population based estimates of obstructive sleep apnea (OSA) frequency and health impact are incomplete. The aim of this study was to determine the prevalence of risk factors for physician and sleep study diagnosed OSA among individuals in a state-based surveillance program METHODS: Using questions inserted into the 2016 (n = 5,564) and 2017 (n = 10,884) South Carolina Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention, we analyzed the prevalence of physician diagnosed OSA and associated comorbidities. The validated STOP-BANG questionnaire without neck circumference (STOP-BAG) defined populations at moderate risk (score 3–4) and high risk (score 5–7). Statistical analysis using weighted prevalence and means and their 95% confidence intervals (CI) thus reflect population estimates of disease burden. RESULTS: The population-based prevalence of physician diagnosed OSA in South Carolina was 9.7% (95% CI: 9.0–10.4). However, the populations with moderate risk (18.5%, 95% CI: 17.3–19.8) and high risk (25.5%, 95% CI: 23.9–27.1) for OSA, as determined by the STOP-BAG questionnaire, were much higher. Compared to those at low risk for OSA, those at high risk were more often diagnosed with coronary heart disease, stroke, asthma, skin cancer, other cancers, chronic obstructive pulmonary disease, arthritis, depression, kidney disease, and diabetes (all P < .001). CONCLUSIONS: OSA is common and strongly associated with major comorbidities. As such, this public health crisis warrants more diagnostic and therapeutic attention. The STOP-BAG questionnaire provides a public health platform to monitor this disease. CITATION: Strange C, Richard CL, Shan S, et al. A population-based estimate of the health care burden of obstructive sleep apnea using a STOP-BAG questionnaire in South Carolina. J Clin Sleep Med. 2021;17(3):367–374.

Prescribers and asthma patients should know that ICS/LABA combination inhalers used as reliever therapy may expire under patient use sooner than the expiration shown on the inhaler, compromising effectiveness if not considered by the prescriber and patienthttps://bit.ly/3fhHMX2

BACKGROUND: Internationally, adult asthma medication adherence rates are low. Studies characterizing variations in barriers by country are lacking. OBJECTIVE: To conduct a scoping review to characterize international variations in barriers to asthma medication adherence among adults. METHODS: MEDLINE, EMBASE, Web of Science (WOS), and CINAHL were searched from inception to February 2017. English-language studies employing qualitative methods (eg, focus groups, interviews) were selected to assess adult patient- and/or caregiver-reported barriers to asthma medication adherence. Two investigators independently identified, extracted data, and collected study characteristics, methodologic approach, and barriers. Barriers were mapped using the Theoretical Domains Framework and findings categorized according to participants’ country of residence, countries’ gross national income, and the presence of universal health care (World Health Organization definitions). RESULTS: Among 2942 unique abstracts, we reviewed 809 full texts. Among these, we identified 47 studies, conducted in 12 countries, meeting eligibility. Studies included a total of 2614 subjects, predominately female (67%), with the mean age of 19.1 to 70 years. Most commonly reported barriers were beliefs about consequences (eg, medications not needed for asthma control, N [ 29, 61.7%) and knowledge (eg, not knowing when to take medication, N = 29, 61.7%) and knowledge (eg, not knowing when to take N = 27, 57.4%); least common was goals (eg, asthma not a priority, N = 1, 2.1%). In 27 studies conducted in countries classified as high income (HIC) with universal health care (UHC), the most reported barrier was participants’ beliefs about consequences (N = 17, 63.3%). However, environmental context and resources (N = 12, 66.7%) were more common in HIC without UHC. CONCLUSION: International adherence barriers are diverse and may vary with a country’s sociopolitical context. Future adherence interventions should account for trends.

Drug therapies play an integral role in the treatment of both chronic obstructive pulmonary (COPD) and cardiovascular diseases (CVD). Optimizing medication efficacy and safety in these patients is complicated by interrelationships among aging, frequent healthcare encounters, polypharmacy, alterations in drug disposition related to heart disease, aerosol drug delivery, drug interactions, and heightened risks of adverse-effects. In addition to side-effects associated with oral and parenteral therapies, risks of systemic effects associated with inhaled medications must also be considered. Medications commonly used in the treatment of COPD with increased risks of cardiac events include inhaled bronchodilators, anti-infectives, and systemic corticosteroids. On the other hand, respiratory-related adverse effects of cardiac drugs such as non-selective β-blockers, angiotensin converting enzyme inhibitors (ACEI), and anti-arrhythmics are also important considerations. Most prospective clinical trials evaluating the efficacy and safety of inhaled bronchodilators have not found a greater risk of cardiac events, however, patients with CVD are usually excluded. Conversely, retrospective studies of healthcare databases and meta-analysis tend to show an association with inhaled bronchodilators with cardiac events. There are now several prospective studies of COPD patients with significant heart disease that found either minimal, no increased or decreased adverse cardiac effects. Studies show that inhaled bronchodilators can improve cardiac performance in hyper-inflated COPD patients. Partially related to concerns of adverse respiratory effects, the under-prescribing of β-blockers in COPD is an important issue as cardio-selective agents have been shown to reduce mortality in COPD patients with heart disease. Continued basic, translational, and clinical research will provide greater insight into optimizing medication efficacy and safety in this population.

BACKGROUND: COPD guidelines report that systemic corticosteroids are preferred over inhaled corticosteroids in the treatment of exacerbations, but the inhaled route is considered to be an option. OBJECTIVES: To conduct a systematic review and meta-analysis regarding the efficacy and safety of inhaled corticosteroids for COPD exacerbations. The second objective was to provide pharmacologic and clinical perspectives of inhaled corticosteroids for COPD exacerbations. METHODS: The primary outcome was a change in FEV1 baseline versus the last measured value. Secondary outcomes were a change in (PaO2) and (PaCO2) baselines versus the last measured values; FEV1, PaO2, and PaCO2 at 24 or 72 h; and hyperglycemia. RESULTS: Each of the 9 studies included in the meta-analysis was conducted in subjects who were hospitalized and not critically ill. Our meta-analysis indicated that high-dose nebulized budesonide 4–8 mg/d was noninferior to systemic corticosteroids on the change in FEV1 between baseline and the last measured value (mean difference of 0.05, 95% CI −0.01 to 0.12, P = .13) and PaCO2 (mean difference of −1.14, 95% CI −2.56 to 0.27, P = .11) but of inferior efficacy for PaO2 changes (mean difference of −1.46, 95% −2.75 to −0.16, P = .03). Hyperglycemia was less frequent with high-dose nebulized budesonide (risk ratio, 0.13; 95% CI 0.03–0.46; P = .002). CONCLUSIONS: Based on our meta-analysis with a change in FEV1 as the primary end point, high-dose nebulized budesonide was an acceptable alternative to systemic corticosteroids in hospitalized subjects with COPD exacerbations who were not critically ill. Additional well-designed prospective studies are needed in both the acute care and ambulatory settings. We provide perspective on how this evidence might be applied in clinical practice.

Objective: To review the pharmacology, efficacy, and safety of the first nebulized long-acting muscarinic antagonist (LAMA), glycopyrrolate (GLY)/eFlow closed system (CS) nebulizer, approved for maintenance treatment of chronic obstructive pulmonary disease (COPD). Data Sources: A PubMed search was conducted (January 2000 to July 2018) using the following terms/phrases: nebulized glycopyrrolate, inhalation devices in COPD, long-acting muscarinic antagonists COPD, and COPD survey. Retrieved articles were reviewed to identify additional references. Study Selection and Data Extraction: Primary and review articles on GLY/eFlow CS and other treatment options for patients with COPD were selected. Data Synthesis: Guidelines recommend the use of LAMAs, alone or in combination with long-acting β2-agonists, as maintenance therapy for the majority of patients with COPD. With the range of different devices and bronchodilators now available, treatment can be tailored based on individual needs. The eFlow CS nebulizer delivers GLY rapidly over a 2- to 3-minute period and provides bronchodilation within 30 minutes, lasting 12 hours. Phase 2 dose-finding and phase 3 studies demonstrated sustained statistically significant and clinically important improvements in pulmonary function and patient-reported outcomes with GLY/eFlow CS. Relevance to Patient Care and Clinical Practice: GLY/eFlow CS provides a novel, portable, efficient, and rapid drug delivery system. Conclusions: The recently approved GLY/eFlow CS drug-device combination provides a viable treatment option for patients with COPD, particularly those with conditions that may impair proper use of traditional handheld inhalers.

Drug delivery by inhalation is the principal strategy to treat obstructive lung diseases, which affect about 15% of the population in the United States. Aerosol delivery devices have evolved over more than 60 years from the basic pressurized metered-dose inhaler and nebulizer to numerous types of inhalers and devices, including valved holder chambers, dry powder inhalers, soft mist inhalers, as well as smart inhalers and nebulizers. Although these devices improve a patient's ability to self-administer medication, many problems with optimal delivery still exist. Appropriate selection and repeated patient education can help lessen the problems with these devices. Aerosol science is evolving, with methods of measurement that include radio-scintigraphy and magnetic resonance imaging, to provide a better understanding of aerosol delivery and effects. Understanding the science and clinical application of aerosol drug delivery can substantially aid clinicians in optimizing these therapies for their patients.

The novel, easy-to-use, breath-actuated fluticasone propionate/salmeterol multidose dry powder inhaler (MDPI) (AirDuo RespiClick®) was recently approved in the USA for twice-daily treatment of asthma in patients aged ≥ 12 years. This inhaled corticosteroid (ICS) and long-acting β2-adrenoreceptor agonist (LABA) combination treatment is available in low-, mid- and high-dosage formulations (55/14, 113/14 and 232/14 μg, respectively). In 12-week, phase III trials in patients aged ≥ 12 years with persistent asthma, all three dosages of fluticasone propionate/salmeterol MDPI treatment produced significant improvements in lung function and other asthma symptoms compared with fluticasone propionate MDPI monotherapy or placebo MDPI. In a 26-week, phase III trial in this patient population, mid- and high-dosage fluticasone propionate/salmeterol MDPI were noninferior to mid- (250/50 μg) and high- (500/50 μg) dosage fluticasone propionate/salmeterol DPI (Advair Diskus®), respectively, in terms of improvements in lung function. Treatment-emergent adverse events (TEAEs) with fluticasone propionate/salmeterol MDPI were mostly of mild to moderate severity, with no severe TEAEs deemed to be treatment related. Although long-term pharmacovigilance is required to fully establish its safety, given the ease of use and favorable characteristics of the device and its clinical efficacy at relatively low metered doses of the active moieties, fluticasone propionate/salmeterol MDPI is an important emerging treatment option in patients aged ≥ 12 years with asthma.

Low adherence and poor outcomes provide opportunity for digital coaching to engage patients with uncontrolled asthma in their care to improve outcomes.To examine the impact of a remote digital coaching program on asthma control and patient experience.We recruited 51 adults with uncontrolled asthma, denoted by albuterol use of2 times per week and/or exacerbations requiring corticosteroids, and applied a 12-week patient-centered remote digital coaching program using a combination of educational pamphlets, symptom trackers, best peak flow establishment, physical activity, and dietary counseling, as well as coaches who implemented emotional enforcement to motivate disease self-management through telephone, text, and email. Baseline and post-intervention measures were quality of life (QOL), spirometry, Asthma Control Test (ACT), Asthma Symptom Utility Index (ASUI), rescue albuterol use, and exacerbation history.Among 51 patients recruited, 40 completed the study. Eight subjects required assistance reading medical materials. Significant improvements from baseline were observed for Patient-Reported Outcomes Measurement Information System mental status (p = 0.010), body weight, and outpatient exacerbation frequency (p = 0.028). The changes from baseline in ACT (p = 0.005) were statistically significant but did not achieve the pre-specified minimum clinically important difference (MCID), whereas for ASUI, the MCID and statistical significance were achieved. Spirometry and rescue albuterol use were no different.A patient-oriented, remote digital coaching program that utilized trained health coaches and digital materials led to statistically significant improvement in mental status, outpatient exacerbations, body weight, and ASUI. Digital coaching programs may improve some outcomes in adults with uncontrolled asthma.

Background The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population. Methods Pubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals. Results Seventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10–1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality. Conclusions Our results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2263-6) contains supplementary material, which is available to authorized users.

Introduction: A challenge when managing asthma patients is the lack of reliable information about inhaler technique. ProAir Digihaler (Teva Pharmaceuticals, Israel), with integrated sensors, can accurately measure inhalation parameters, thereby recording objective information on inhaler use and technique. This analysis aimed to identify and characterize issues related to inhaler technique by using data from the integrated electronic Digihaler. Methods: A 12-week, open-label study was conducted with ProAir Digihaler (salbutamol 90 mcg 1–2 inhalations every 4 hours as needed) among patients (≥18 years) with exacerbation-prone asthma. The electronic component of Digihaler recorded inhalation variables that were downloaded for analyses at the study end. Results: Of 370 patients who used Digihaler at least once, 360 (97.3%) patients made ≥1 valid inhalations. There were 53,374 attempted doses. Mean (SD) peak inhalation flow (PIF) was 76.8 (29.3) L/min, inhalation volume 1.44 (0.92) L, time to PIF 0.52 (0.45) s and inhalation duration 1.53 (0.88) s. Incorrect use was identified by the detection of very low inhalation flow ( Conclusions: Digihaler offers opportunities to identify and correct real-life problems with inhaler technique, thereby increasing the chances of improving treatment outcomes. Studies are ongoing to evaluate Digihaler with a companion mobile app that provides patient feedback to potentially help improve inhaler use.

Objective: Provide information for pharmacists on idiopathic pulmonary fibrosis (IPF) and its treatment. Study Selection and Data Extraction: All articles with data from randomized controlled trials of nintedanib or pirfenidone were reviewed. Data Synthesis: IPF is a progressive and ultimately fatal interstitial lung disease characterized by decline in lung function and worsening dyspnea. It is uncommon and mainly occurs in individuals aged >60 years, particularly men with a history of smoking. Nintedanib and pirfenidone were approved in the United States for the treatment of IPF in 2014 and received conditional recommendations in the 2015 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association treatment guidelines. These drugs slow the progression of IPF by reducing the rate of decline in lung function. Their adverse event profile is characterized mainly by gastrointestinal events, which can be managed through dose adjustment and symptom management. Management of IPF should also include smoking cessation, vaccinations, and supportive care such as patient education, pulmonary rehabilitation, and the use of supplemental oxygen as well as optimizing the management of comorbidities. Relevance to Patient Care and Clinical Practice: This review provides clinical pharmacists with information on the course of IPF, what can be expected of current treatments, and how to help patients manage their drug therapy. Conclusions: IPF is a progressive disease, but treatments are available that can slow the progression of the disease. Clinical pharmacists can play an important role in the care of patients with IPF through patient education, monitoring medication compliance and safety, ensuring drugs for comorbidities are optimized, and preventive strategies such as immunizations.

Chronic obstructive pulmonary disease (COPD) can be a disabling disease, and the impact on older adults is particularly evident in the nursing home setting. Chronic obstructive pulmonary disease is present in about 20% of nursing home residents, most often in women, and accounts for significant healthcare utilization including acute care visits for exacerbations and pneumonia, as well as worsening heart disease and diabetes mellitus. The emphasis on hospital readmissions is particularly important in nursing homes where institutions have quality measures that have financial implications. Optimizing drug therapies in individuals with COPD involves choosing medications that not only improve symptoms, but also decrease the risk of exacerbations. Optimizing the treatment of comorbidities such as heart disease, infections, and diabetes that may affect COPD outcomes is also an important consideration. Depending on the nursing home setting and the patient, the options for optimizing COPD drug therapies may be limited owing to patient-related factors such as cognition and physical impairment or available resources, primarily reimbursement-related issues. Choosing the best drug therapy for COPD in older adults is limited by the difficulty in assessing respiratory symptoms using standardized assessment tools and potentially decreased inspiratory ability of frail individuals. Because of cognitive and physical impediments, ensuring optimal delivery of inhaled medications into the lungs has significant challenges. Long-acting bronchodilators, inhaled corticosteroids, and roflumilast decrease the risk of exacerbations, although inhaled corticosteroids should be used judiciously in this population because of the risk of pneumonia and oropharyngeal side effects. Treatment of COPD exacerbations should occur early and consideration should be made to the benefits and risks of systemic corticosteroids and antibiotics. Clinical research in the COPD population in nursing homes is clearly lacking, and ripe for discovery of effective management strategies.

Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. Methods: Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as &ge, 10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease burden was defined by respiratory symptoms and health impairments. Data were analyzed using multiple logistic regression models with age as a covariate. Results: Among 35,722 adults &ge, 18 years, the overall prevalence of COPD and high-risk for COPD were 6.6% and 5.1%. Differences among COPD risk groups were evident based on gender, race, age, geography, tobacco use, health impairments, and respiratory symptoms. Risk for disease was seen early where 3.75% of 25&ndash, 34 years-old met high-risk criteria. Longer tobacco duration was associated with an increased prevalence of COPD, particularly &gt, 20 years. Seventy-nine percent of persons &ge, 45 years-old with frequent shortness of breath (SOB) reported having or being at risk of COPD, reflecting disease burden. Conclusion: These data, representing nearly 18% of US adults, indicates those at high risk for COPD share many, but not all of the characteristics of persons diagnosed with the disease and demonstrates the value of the BRFSS as a tool to define lung health at a population level.

Background The epidemiology of Interstitial Lung Diseases (ILD) in the Veterans Health Administration (VHA) is presently unknown. Research question Describe the incidence/prevalence, clinical characteristics, and outcomes of ILD patients within the Veteran’s Administration Mid-Atlantic Health Care Network (VISN6). Study design and methods A multi-center retrospective cohort study was performed of veterans receiving hospital or outpatient ILD care from January 1, 2008 to December 31st, 2015 in six VISN6 facilities. Patients were identified by at least one visit encounter with a 515, 516, or other ILD ICD-9 code. Demographic and clinical characteristics were summarized using median, 25th and 75th percentile for continuous variables and count/percentage for categorical variables. Characteristics and incidence/prevalence rates were summarized, and stratified by ILD ICD-9 code. Kaplan Meier curves were generated to define overall survival. Results 3293 subjects met the inclusion criteria. 879 subjects (26%) had no evidence of ILD following manual medical record review. Overall estimated prevalence in verified ILD subjects was 256 per 100,000 people with a mean incidence across the years of 70 per 100,000 person-years (0.07%). The prevalence and mean incidence when focusing on people with an ILD diagnostic code who had a HRCT scan or a bronchoscopic or surgical lung biopsy was 237 per 100,000 people (0.237%) and 63 per 100,000 person-years respectively (0.063%). The median survival was 76.9 months for 515 codes, 103.4 months for 516 codes, and 83.6 months for 516.31. Interpretation This retrospective cohort study defines high ILD incidence/prevalence within the VA. Therefore, ILD is an important VA health concern.

The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and etiologies, it is also associated with worsened COPD health outcomes. Effective interventions in these people are needed to decrease these disparities. Efforts that may help lessen these health inequities in low SES include 1) better surveillance targeting diagnosed and undiagnosed COPD in disadvantaged people, 2) educating the public and those involved in health care provision about the disease, 3) improving access to cost-effective and affordable health care, and 4) markedly increasing the efforts to prevent disease through smoking cessation, minimizing use and exposure to BF, and decreasing occupational exposures. COPD is considered to be one the most preventable major causes of death from a chronic disease in the world; therefore, effective interventions could have a major impact on reducing the global burden of the disease, especially in socioeconomically disadvantaged populations.

Rationale: The asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) occurs in patients with fixed airway obstruction that defines COPD and with symptoms more typical of asthma. ACOS prevalence and the comorbidities associated with this syndrome have been inadequately characterized.Objectives: Because this population is prone to more frequent exacerbations, we hypothesized that comorbidities associated with ACOS are higher than those with COPD, asthma, and control populations in the United States.Methods: We examined the self-reported demographics, smoking status, comorbidities, and hospitalization or emergency department (ED) visitation experience among study respondents older than 35 years of age (n = 90,851) in the Behavioral Risk Factor Surveillance System survey and compared participants with ACOS to COPD, asthma, and control groups. We used logistic regression to compare ACOS and COPD populations to model the impact of comorbid conditions and hospitalization/ED visits after adj...

A number of new agents for the management of chronic obstructive pulmonary disease (COPD) are at different stages of development, including several inhaled long-acting antimuscarinics (LAMA). Long-acting bronchodilators are considered to be central to the management of COPD due to the evidence supporting their efficacy and safety. Umeclidinium, a LAMA, has recently been approved for the maintenance treatment of moderate to very severe COPD in a number of countries. This comprehensive review and pooled meta-analysis provides detailed information about the efficacy and safety of this agent. The pharmacokinetics and pharmacodynamics of umeclidinium observed in phase I and II studies support its once-daily administration. Umeclidinium is rapidly cleared from blood, and renal or hepatic impairment do not lead to significant changes in drug disposition. A pooled analysis of phase III and comparative studies of umeclidinium in patients with moderate to very severe COPD showed significant improvement in lung function measures, including trough forced expiratory volume in 1 s (FEV1), as well as in acute exacerbations of COPD, dyspnea, and quality of life. Adverse effects, including known anticholinergic effects, were uncommon with umeclidinium. Limited data suggest the efficacy of umeclidinium is similar to that of tiotropium. Umeclidinium is administered as a dry powder inhaler, provides adequate lung delivery in patients with moderate to very severe airflow obstruction, and appears to be easily used by patients. Umeclidinium provides a safe and effective option as an inhaled LAMA for the management of COPD.

Aims/Objectives: Given the high prevalence of tobacco use, the VA, the largest US healthcare system, is an enriched population for IIP and E. Our objective was to characterize comorbidities, pack year history(PYH), tobacco duration(TY), years between quitting and diagnosis(YQ), diagnosis(Dx) date, supplemental oxygen(02), and deaths among 4 groups:1) IIP with E (IIP+E), 2) IIP without E (IIP-E), 3) lung granuloma(LG) with E (LG+E), and 4) LG without E (LG-E). Methods: Among 3154 patients receiving care for ICD9 515,516 codes at 6 VA centers from 2008-2015, we identified 849 subjects with either IIP or LG(no ILD) based on electronic/manual data extraction and computed tomography. Results: Between IIP+/-E and LG+/-E groups, age at Dx and time from Dx to death were similar. Though the time from Dx to death was similar, the proportion alive 5 yr after Dx was lower in both IIP groups. Mean TY, YQ, and PYH differed among groups. Pulmonary hypertension, diabetes and 02 were more frequent in IIP groups, while lung cancer was greater in the +E groups. Conclusion: In one of the largest reported cohorts of IIP+E, we provide tobacco use data not previously reported and outcomes in a high-prevalence cohort.

Although inhaled therapies are typically preferred for the maintenance treatment of obstructive lung diseases, oral drug therapies can also play valuable roles. The most commonly used oral agents are phosphodiesterase inhibitors, theophylline, macrolides, leukotriene modifiers, and mucoactive agents. Advantages of these oral agents include the unique pharmacologic mechanisms of action, the avoidance of the challenges of proper inhalational lung administration, and, in most instances, relative drug cost. For many of these agents, anti-inflammatory or immunomodulatory effects are the predominant pharmacologic mechanism that each provides clinical benefit, with the exception of guaifenesin. In addition, theophylline, leukotriene modifiers, chronic macrolides, phosphodiesterase inhibitors, and N-acetylcysteine have been shown to decrease exacerbations in obstructive lung disease. Fairly rapid bronchodilation occurs with the phosphodiesterase inhibitors, theophylline, and leukotriene modifiers, although less than that achieved with inhaled therapies. The clinical roles of phosphodiesterase inhibitors, specifically roflumilast, and macrolides continues to be defined today, whereas the roles theophylline and leukotriene modifiers have probably been largely delineated. Azithromycin is the principal macrolide used chronically for obstructive lung diseases, especially COPD. Although guaifenesin is used widely, its effectiveness is unclear, whereas N-acetylcysteine currently has strong evidence supporting a decreased risk of COPD exacerbations. Mucolytic agents like N-acetylcysteine are used more widely outside the United States in obstructive lung diseases.

The novel, easy-to-use, breath-actuated fluticasone propionate/salmeterol multidose dry powder inhaler (MDPI) (AirDuo RespiClick

We assessed the clinical features and treatment of pediatric patients with drug-induced anaphylaxis in clinical settings. Pediatric drug-induced anaphylaxis cases collected by the Beijing Pharmacovigilance Database from 2004 to 2014 were analyzed. A total of 91 cases were identified. Drug-induced anaphylaxis was primarily caused by antibiotics (53%). Children of 0–5 years were more likely to develop cyanosis symptoms than children of 13–17 years (OR = 5.14, 95%CI [1.74, 15.20], P = 0.002). Children of 13–17 years were more likely to develop hypotension than children of 6–12 years (OR = 11.79, 95%CI [2.28, 60.87], P = 0.002), and to manifest both neurological symptoms (OR = 3.56, 95%CI [1.26, 10.08], P = 0.015) and severe anaphylaxis than children of 0–5 years (OR = 15.46, 95%CI [1.85, 129.33], P = 0.002). Supratherapeutic doses of epinephrine were more likely with intravenous (IV) bolus (92%) in contrast to either intramuscular (IM) (36%, OR = 19.25, 95%CI [1.77, 209.55], P = 0.009) or subcutaneous (SC) injections (36%, OR = 19.80, 95% CI [1.94, 201.63], P = 0.005). Only 62 (68%) patients received epinephrine treatment as the first-line therapy. Conclusion: This study demonstrates that antibiotics were the most common cause of pediatric drug-induced anaphylaxis. Children may present with different anaphylactic signs/symptoms based on age groups. Epinephrine is under-utilized and provider education on the proper management of drug-induced anaphylaxis is warranted. What is Known: • The most common causes of anaphylaxis in children are allergies to foods. Drugs are the second most common cause of pediatric anaphylaxis. • IM epinephrine is the recommended initial treatment of anaphylaxis. What is New: • Drug-induced anaphylaxis in pediatric patients has age-related clinical features. • IV bolus epinephrine was overused and associated with supratherapeutic dosing. Electronic supplementary material The online version of this article (10.1007/s00431-017-3048-z) contains supplementary material, which is available to authorized users.