Interventional Chest/Diagnostic Procedures
Review of The AMPLE Trial: is talc making a comeback?
A proposed advantage of indwelling pleural catheters (IPC) is their purported ability to reduce hospitalization time when compared with the more traditional talc pleurodesis procedure. The recently published AMPLE trial was a multicenter randomized trial comparing the impact of IPCs vs talc pleurodesis on hospitalization days in patients with malignant pleural effusions. One-hundred forty-six patients were randomized for pleurodesis to either IPC vs pleurodesis via talc slurry in nine centers in Australia, New Zealand, Singapore, and Hong Kong. Patients were followed for up to 12 months. Secondary outcomes included need for further pleural intervention, breathlessness, quality of life, and adverse events.
Patients randomized to IPC spent on average 2 days less in the hospital (10 vs 12 days), a difference that was statistically significant, though of questionable clinical relevance, and somewhat disappointing in light of a prior prospective study from the same group suggesting a benefit of 6 to 7 days (Fysh. Chest. 2012;142[2]:394. As in previous studies, additional pleural procedures were more common in the talc group, adverse events occurred more frequently with IPC, but breathlessness and quality of life were identical in both groups.
This study raises interesting questions. Clearly, IPCs have been favored over talc pleurodesis in the US in the last decade, primarily because of a perceived benefit in terms of hospitalization time. In the absence of clear advantage of IPC on time spent in the hospital, impact on breathlessness and quality of life, and considering the inconvenience of frequent drainage, co-pay incurred by patients, and increased adverse events with IPC, the pendulum may swing again toward talc pleurodesis.
Christine Argento, MD, FCCP
Fabien Maldonado, MD, FCCP
Steering Committee Members
Pediatric Chest Medicine
Early escalation of inhaled corticosteroids: does it help prevent asthma exacerbations?
Asthma is one of the most common chronic conditions in children. The importance of effective control of asthma to prevent exacerbations is well accepted. Inhaled corticosteroids (ICS) are a preferred component of treatment to improve asthma control in children with persistent asthma; however, exacerbations can still occur and result in significant morbidity. Most patients receive systemic corticosteroids during acute asthma exacerbations. The most recent Global Initiative for Asthma (GINA) guidelines recommend increasing ICS at the first signs of an asthma exacerbation in an effort to lessen the need for systemic corticosteroids (GINA. Global strategy for asthma management and prevention. 2017. http://www.ginasthma.org/).
In a recent issue of the New England Journal of Medicine, Jackson and colleagues at the National Heart, Lung, and Blood Institute AsthmaNet published the results of a randomized, double-blind 48-week trial, which included 254 children between ages 5 and 11 years with mild-moderate asthma. Their objectives were to compare exacerbation rates, time to first exacerbation, acute care visits, and bronchodilator use in children randomized to treatment with either high (5 x baseline ICS dose x 7 days) or low dose inhaled corticosteroids early in a drop to the “yellow zone” (Jackson, et al. N Engl J Med. 2018;378[10]:891).
Time to asthma exacerbations and exacerbations that required treatment with corticosteroids did not significantly differ between the low dose and high dose groups. Unexpectedly, the rate of exacerbations was higher with the high dose compared with the low dose group (0.48 vs 0.37). The children who were in the high dose group received 16% more ICS compared with the low dose group. Although not significant, there was a lower linear growth rate, ~0.23 cm per year seen in this high-dose group than in the low-dose group. Additionally, the use of bronchodilator, symptoms, and the rates of evaluation by a physician (ie, emergency department or urgent care visits) did not significantly differ between the two groups.
This study was specific to school-age children with mild-moderate persistent asthma treated with low dose ICS with a history of good adherence. Overall, this well-designed study helps address a question that many clinicians have regarding escalating ICS in the “yellow zone.” Escalating ICS did not reduce exacerbations at the cost of a lower linear growth rate. When it comes to escalating ICS for asthma exacerbation, more is not better.
In conclusion, in children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129).
John Bishara, DO
Fellow-in-Training Member