Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

An evaluation of negative reinforcement to increase self-feeding and self-drinking for children with feeding disorders.

Self-feeding with utensils represents an important step in a child's progression toward age-typical eating and emerges in the absence of intervention for most children. In contrast, children with feeding disorders may lack the skill or motivation to self-feed, which impedes progress toward age-typical eating. In the current study, experimenters used a multielement design to evaluate negative reinforcement in the form of meal termination to transition six participants with a feeding disorder from caregiver-fed to self-fed bites and drinks. Caregivers conducted meals in which they fed the participant or prompted them to self-feed. During self-fed meal-termination sessions, participants had the opportunity to end the meal contingent on self-feeding the presented bite(s) or drink(s). Self-feeding increased during meal-termination sessions for all participants. The experimenters discuss these results relative to their potential to inform interventions for children with feeding disorders that progress the child toward age-typical eating.

Relapse during the treatment of pediatric feeding disorders.

Resurgence and renewal are treatment-relapse phenomena in which previously extinguished behavior returns after the conditions for an alternative response worsen or the context changes, respectively. Recently, researchers have evaluated the prevalence of resurgence and renewal when treating destructive behavior with functional communication training. However, resurgence of inappropriate mealtime behavior has yet to be evaluated; perhaps because treatments involve qualitatively different resurgence opportunities (e.g., increased bite-presentation rate). We evaluated the prevalence of resurgence and renewal of inappropriate mealtime behavior across 22 and 25 applications of extinction-based treatments, respectively. Resurgence occurred in 41% (9/22) of applications, most often following presentation-rate increases. Renewal occurred in 52% (13/25) of applications, most often following feeder changes from therapist to caregiver. We discuss these findings in terms of their ability to inform relapse-mitigation strategies for resurgence and renewal of inappropriate mealtime behavior.

On the scope and characteristics of relapse when treating severe destructive behavior.

Prior studies on treatment relapse have typically examined the prevalence of resurgence or renewal of target behavior (e.g., destructive behavior) in isolation. This study analyzed both types of relapse during 25 consecutive treatments involving functional communication training during worsening reinforcement conditions for alternative behavior (i.e., schedule thinning) or following context changes. We also examined disruption of alternative behavior (i.e., functional communication requests, compliance). Resurgence and renewal of destructive behavior occurred in 76% and 69% of treatments, respectively, and in approximately a third of changes in reinforcement or context. Relapse of destructive behavior predicted alternative-response disruption and vice versa; the co-occurrence of these two events always exceeded the background probabilities of either event occurring in isolation. General reductions in treatment efficacy occurred across changes in reinforcement or context, with no apparent decrease in likelihood in later transitions. We discuss implications of our findings with respect to future studies examining treatment durability.

An evaluation of a renewal-mitigation procedure for inappropriate mealtime behavior.

Renewal, the increase in behavior during extinction following context changes, may be particularly concerning during intervention for feeding disorders because context changes are often necessary for intervention generality and maintenance (Podlesnik et al., 2017). In the current study, we tested for renewal and evaluated a renewal-mitigation procedure when we transferred intervention from a therapist to a caregiver, from clinic to the home, and changed the foods the feeder presented. We used an ABA arrangement to evaluate the generality of the renewal effect with 7 participants who engaged in inappropriate mealtime behavior. Context A was functional reinforcement. Context B was function-based extinction during the control and mitigation conditions and our renewal-mitigation procedure in the mitigation condition. The renewal test was function-based extinction in Context A. We observed renewal of inappropriate mealtime behavior in 4 of 7 participants, and our renewal-mitigation procedure was effective for 4 of 4 participants.

Pediatric Prevention: Feeding Disorders.

Applied behavior analysis has the most empirical support as intervention for pediatric feeding disorders, when a child does not eat or drink a sufficient quantity or variety of food to maintain proper nutrition. Interdisciplinary collaboration is crucial for diagnosis, referral, and management of pediatric feeding disorders because the etiology is complex and multifactorial. Thus, our aim is to provide information about how to recognize a feeding disorder, to delineate the environmental variables implicated in the etiology and maintenance of feeding disorders, and to provide recommendations for prevention and intervention for feeding disorders based on the applied-behavior analytic literature.

Overcoming beta-agonist tolerance: high dose salbutamol and ipratropium bromide. Two randomised controlled trials.

BACKGROUND: Asthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide. METHODS: Two double-blind, placebo-controlled, crossover studies of inhaled formoterol 12 mug twice daily in patients with asthma.High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 5 mg was then administered via nebuliser and the FEV1 was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV1. Salbutamol 200 mug or ipratropium bromide 40 mug was then inhaled and the FEV1 was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV1, dose of provocational agent and FEV1 fall during the challenge procedure. RESULTS: The response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo (95% confidence 5 to 25%, p = 0.008). The response to ipratropium was unchanged. CONCLUSION: Long-acting beta-agonist treatment induces tolerance to the bronchodilator effect of beta-agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected.

Recovery from bronchoconstriction and bronchodilator tolerance.

Until recently, researchers believed that tolerance or tachyphylaxis to the bronchodilator effects of beta-agonists did not occur. However, recent studies examining the recovery from bronchoconstriction have clearly shown that an impaired response to beta-agonists occurs in patients who have been using regular beta-agonist treatment. This tolerance develops with both long- and short-acting beta-agonists and is not affected by treatment with inhaled steroids. It develops rapidly, reaching a maximum within 1 wk of starting beta-agonists, and has been demonstrated after methacholine, hypertonic saline, mannitol, and exercise-induced bronchoconstriction. The observed reduction in the bronchodilator response is proportional to the severity of bronchoconstriction. Therefore, although individuals with stable asthma show little evidence of tolerance, those with severe bronchospasm have a markedly reduced bronchodilator response to beta-agonists. Almost all asthmatics show evidence of tolerance when tested in the setting of bronchoconstriction, although the extent of this tolerance varies. The reasons for this interindividual variation are not understood. Bronchodilator tolerance is difficult to study in the clinical setting because nearly every patient has used multiple doses of beta-agonist before seeking medical attention. However, there is compelling evidence that the response to rescue beta-agonist treatment is reduced in those who use regular long- or short-acting beta-agonists. The extent to which this phenomenon contributes to asthma morbidity and mortality remains to be determined.

Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial.

BACKGROUND: Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. METHODS: Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 microg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 microg (cumulative dose) was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve. RESULTS: The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68%) lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001). CONCLUSION: The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.

Rapid onset of tolerance to beta-agonist bronchodilation.

INTRODUCTION: Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This is easily demonstrated if dilation is tested following methacholine challenge. It is not known how quickly tolerance develops or how long it lasts after stopping beta-agonist therapy. METHODS: Ten subjects with stable asthma were studied. Following 2 weeks without beta-agonists, methacholine was inhaled to induce a 20% reduction in FEV1. The response to inhaled salbutamol (100, 100, 200 microg at 5-min intervals) was then measured. This procedure was repeated 24 h after one dose and 24 h after 3, 7 and 14 days of inhaled formoterol 12 microg twice daily, and 3 and 5 days after formoterol was discontinued. Unscheduled use of beta-agonists was not permitted. RESULTS: Bronchodilator tolerance, assessed by a reduction of the area under the salbutamol dose-response curve, occurred after 1 dose of formoterol (28% reduction, 95% CI 12, 45%), increased up to 1 week and plateaued between 1 and 2 weeks (58% reduction, 95% CI 38, 78%). Three days after stopping formoterol, the response to salbutamol was similar to baseline (12% reduction, 95% CI -9, 33%). The first dose of formoterol provided significant bronchoprotection to methacholine (1.6 doubling doses, P=0.007). This diminished with regular treatment and by 2 weeks the PD20 methacholine was not significantly different to baseline. CONCLUSIONS: Bronchodilator tolerance occurs after a single dose and reaches a maximum after 1 week of regular formoterol. Sensitivity recovers 3 days after stopping treatment.

A sanguine experience: Case Report.

A 68-year-old man presents at A&E with breathlessness but no chest pain, haemoptysis or sputum production http://ow.ly/R029n.