Impact of Payor-Initiated Switching of Inhaled Corticosteroids on Lung Function.

OBJECTIVES: To evaluate the impact of a payor-initiated formulary change in inhaled corticosteroid coverage on lung function in patients with asthma and on provider prescribing practices. This formulary change, undertaken in August 2016 by a Medicaid payor in Kentucky, eliminated coverage of beclomethasone dipropionate, a metered dose inhaler (MDI), in favor of mometasone furoate, available as MDI and dry powder inhaler (DPI). STUDY DESIGN: A retrospective chart review was conducted on children with asthma ages 6-18 years covered by the relevant payor from a university-based pediatric practice who were seen before the formulary change (February to July 2016) and after (February to July 2017). Spirometry data from each visit was compared using the paired Student t test. RESULTS: Fifty-eight patients were identified who were initially on beclomethasone dipropionate and had spirometry available at both visits. Those who switched from an MDI to a DPI (n = 24) saw a decline in median predicted forced expiratory volume in 1 second from 98.5% to 91% (P = .013). A decline was also seen in forced expiratory flow at 25%-75%, from 89.5% predicted to 76% predicted (P = .041). No significant changes were observed in children remaining on an MDI. Seven patients discontinued inhaled corticosteroid therapy. CONCLUSIONS: This study suggests insurance formulary changes leading to use of a different inhaler device may have a detrimental impact on pediatric lung function, which may be a surrogate measure for overall asthma control. This could be due to a lack of adequate timely educational intervention as well as the inability of some children to use DPIs.

How group structure impacts the numbers at risk for coronary artery disease: polygenic risk scores and nongenetic risk factors in the UK Biobank cohort.

The UK Biobank (UKB) is a large cohort study that recruited over 500,000 British participants aged 40-69 in 2006-2010 at 22 assessment centers from across the United Kingdom. Self-reported health outcomes and hospital admission data are 2 types of records that include participants' disease status. Coronary artery disease (CAD) is the most common cause of death in the UKB cohort. After distinguishing between prevalence and incidence CAD events for all UKB participants, we identified geographical variations in age-standardized rates of CAD between assessment centers. Significant distributional differences were found between the pooled cohort equation scores of UKB participants from England and Scotland using the Mann-Whitney test. Polygenic risk scores of UKB participants from England and Scotland and from different assessment centers differed significantly using permutation tests. Our aim was to discriminate between assessment centers with different disease rates by collecting data on disease-related risk factors. However, relying solely on individual-level predictions and averaging them to obtain group-level predictions proved ineffective, particularly due to the presence of correlated covariates resulting from participation bias. By using the Mundlak model, which estimates a random effects regression by including the group means of the independent variables in the model, we effectively addressed these issues. In addition, we designed a simulation experiment to demonstrate the functionality of the Mundlak model. Our findings have applications in public health funding and strategy, as our approach can be used to predict case rates in the future, as both population structure and lifestyle changes are uncertain.

Impact of elexacaftor/tezacaftor/ivacaftor on respiratory colonization in an adult cystic fibrosis clinic.

BACKGROUND: Little research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa. METHODS: This single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022. Patients were included in the study if they were at least 18 years old with a diagnosis of CF and had at least one month of ETI dispensed, at least one sputum culture obtained, and were currently on ETI. Those who had not been seen since ETI initiation or received a bilateral lung transplant were excluded. The primary outcome was rate of patients with respiratory colonization post-ETI. Colonization was defined as two or more positive P. aeruginosa cultures in a 12-month period. Decolonization was defined as three consecutive negative P. aeruginosa cultures after previous colonization. Key secondary outcomes included average time to discontinuation of mucolytic therapy and relative risk of pulmonary exacerbation. RESULTS: A significant reduction (p<0.001) in colonization with P. aeruginosa was observed with 49 patients in the pre-ETI group compared to 25 in the post-ETI group meeting the definition of colonization (n=79). Average time to discontinuation of mucolytic therapy was 14 months (p=0.002). Relative risk of pulmonary exacerbation was 4.80 (p<0.001). CONCLUSIONS: ETI use resulted in reduced colonization with P. aeruginosa, discontinuation of mucolytic therapy, and decreased frequency of pulmonary exacerbation.

A 13-Year-Old Male Patient With Severe Multifocal Pneumonia and Bronchiectasis That Required Extracorporeal Membrane Oxygenation.

CASE PRESENTATION: A 13-year-old male patient with intermittent asthma and joint hypermobility presented to the ED in acute hypoxemic respiratory distress. He reported experiencing cough, increased work of breathing, and worsening chest pain for 3 days before presentation. He also reported fatigue and decreased appetite for 2 weeks. He had no known fever, myalgias, or recent weight loss. His medical history included two hospitalizations during early childhood for viral respiratory illnesses, one of which required intubation at 8 months of age. He had a gastrostomy tube placed shortly after his hospitalization because of failure to thrive secondary to aspiration based on a swallow study. His weight gain and growth improved with adequate nutrition, and his gastrostomy tube was removed at 2 years of age. His newborn screen, which included immunoreactive trypsinogen, was normal. He was noted to have hypermobile joints on physical examination at a clinic visit in childhood, but his examination results were not concerning for a hypermobility syndrome, and further diagnosis was not pursued. His parents endorsed that he has been a "healthy child" overall other than the occasional cough, which was attributed to asthma. His lifestyle was described as sedentary; he did not play any sports or have any unusual hobbies. He did not take any daily medications and no environmental exposures were reported. There was no family history of pulmonary, autoimmune, or connective tissue disease.

Sterility and Stability Testing of Preservative-free Albuterol.

BACKGROUND: Continuous albuterol administration (CAA) is commonly used in hospitalized patients for treatment of asthma exacerbations. Due to higher dose requirements, CAA requires large volumes of albuterol obtained from multidose vials containing benzalkonium chloride (BAC). BAC is a common pharmaceutical preservative and potent bronchoconstrictor, which may antagonize the bronchodilation effects of albuterol. Some institutions are using preservative-free (PF) albuterol for their CAA. However, no published data currently exist to support the extended sterility or stability of this formulation. OBJECTIVE: To evaluate the sterility and stability of PF-albuterol. METHODS: Sterility testing was conducted for PF- and BAC-albuterol when stored at room temperature. Samples were incubated for 10 days in aerobic and anaerobic blood culture media to assess for bacterial growth. Stability of both albuterol formulations at high (0.67 mg/mL) and low (0.17 mg/mL) concentrations was determined at room temperature and under refrigeration. High performance liquid chromatography was used to evaluate samples up to 168 hours after preparation. RESULTS: No bacterial growth was witnessed from either albuterol formulation at day 10 of observation. Both high and low concentrations of PF-albuterol and BAC-albuterol were stable at room temperature for up to 168 hours. There were no differences in stability between storage conditions for any formulation. CONCLUSIONS: Under the current study conditions, there was no difference in sterility or stability for PF-albuterol when compared with BAC-albuterol. Thus, based on the findings of this study, PF-albuterol is sterile and stable up to 168 hours when stored at room temperature or under refrigerated conditions. The findings of this study do not confirm the therapeutic efficacy of PF-albuterol compared with BAC-albuterol for the treatment of asthma exacerbations. Further studies are warranted to determine the efficacy of PF-albuterol verses BAC-albuterol when used for CAA.

Anti-inflammatory dosing of theophylline in the treatment of status asthmaticus in children.

BACKGROUND: Low-dose theophylline has been recognized for its ability to restore histone deacetylase-2 activity which leads to improved steroid responsiveness and thus improved clinical outcome. We retrospectively evaluated the effect of low-dose theophylline therapy in pediatric patients hospitalized for an acute asthma exacerbation as a proof of concept study. METHODS: We compared patients who received low-dose theophylline (5-7 mg/kg/day) in addition to current standard of care to patients who were treated with current standard of care alone. The primary outcome of the study was hospital length of stay (LOS). Generalized linear mixed-effects modeling (GLMM) was used to test whether receiving theophylline independently predicted outcomes. A Cox (proportional hazards) regression model was also developed to examine whether theophylline impacted LOS. RESULTS: After adjustment for illness severity measures, theophylline significantly reduces LOS (ß=-21.17, P<0.001), time to discontinue oxygen (ß=-15.88, P=0.044), time to spirometric improvement (ß=-16.60, P=0.014), and time to space albuterol (ß=-23.2, P<0.001) as well as reduced costs (ß=-US$2,746, P<0.001). Furthermore, theophylline significantly increased the hazards of being discharged from the hospital (hazards ratio =1.75, 95% confidence interval 1.20-2.54, P=0.004). There was no difference in side effects between patients who receive low-dose theophylline and those who did not. CONCLUSION: The results of this retrospective study suggest low-dose theophylline may have a positive effect in acute status asthmaticus. This study suggests that further research with a prospective, randomized, double-blinded, placebo controlled trial may be warranted to confirm and extend our findings.

Broncholithiasis From Histoplasmosis in a Pediatric Patient: Case Reports and Review of Literature.

Broncholithiasis is a calcification in the airway. Though broncholiths are not common, it is even more unusual in a pediatric patient. We present a 15-year-old immunocompetent pediatric patient who had a broncholith that was found and removed by bronchoscopy.

Loss of asthma control in pediatric patients after discontinuation of long-acting Beta-agonists.

Recent asthma recommendations advocate the use of long-acting beta-agonists (LABAs) in uncontrolled asthma, but also stress the importance of stepping down this therapy once asthma control has been achieved. The objective of this study was to evaluate downtitration of LABA therapy in pediatric patients who are well-controlled on combination-inhaled corticosteroid (ICS)/LABA therapy. Clinical and physiologic outcomes were studied in children with moderate-to-severe persistent asthma after switching from combination (ICS/LABA) to monotherapy with ICS. Of the 54 patients, 34 (63%) were determined to have stable asthma after the switch, with a mean followup of 10.7 weeks. Twenty (37%) had loss of asthma control leading to addition of leukotriene receptor antagonists, increased ICS, or restarting LABA. There were 2 exacerbations requiring treatment with systemic steroids. In patients with loss of control, there was a statistically significant decline in FEV(1) (-8% versus -1.9%, P = 0.03) and asthma control test (-3.2 versus -0.5, P = 0.03). This did not approach significance for FEF(25-75%), exhaled nitric oxide, lung volumes or airway reactivity. No demographic, asthma control measures, or lung function variables predicted loss of control. Pediatric patients with moderate-to-severe persistent asthma who discontinue LABA therapy have a 37% chance of losing asthma control resulting in augmented maintenance therapies. Recent recommendations of discontinuing LABA therapy as soon as control is achieved should be evaluated in a prospective long-term study.