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What Is New In Small Airways Research

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By Ves Dimov, MD
Allergist/Immunologist, Assistant Professor of Medicine and Pediatrics
University of Chicago

Posted 19 December 2012

Detrimental effects on bronchoprotection starts after the 5th dose of albuterol, worsens after 7 doses

Regular use of inhaled β-agonist leads to tolerance to its bronchoprotective effect. This occurs within 12 hours with salmeterol and has been documented at 1 week for salbutamol (the medication name “albuterol” is used in the United States).

This study aimed to determine the course of onset of tolerance to the bronchoprotective effect of salbutamol against methacholine. It was designed as a randomized, double-blind, placebo-controlled trial and included 13 patients with mild asthma. Each treatment period consisted of 7 twice-daily doses (2 puffs of 100 μg of salbutamol or placebo). Methacholine challenges were conducted 24 hours apart on 4 consecutive days, 10 minutes after the first, third, fifth, and seventh doses.

A single dose of salbutamol shifted the methacholine PC20 approximately 5-fold from a geometric mean of 2.1 mg/mL to a geometric mean of 10.7 mg/mL. Maximal bronchoprotection after the active treatment occurred on day 2 after the third dose. After the fifth dose the methacholine PC20 was trending downward, and on day 4 the bronchoprotective effect of salbutamol had significantly decreased from its peak protection.

The authors concluded that the detrimental effects on bronchoprotection after regular use of salbutamol manifest after 5 doses and are significantly reduced from peak protection after 7 doses.

Source: Stewart SL, Martin AL, Davis BE, Cockcroft DW. Salbutamol tolerance to bronchoprotection: course of onset.  Annals of Allergy, Asthma & Immunology 2012; 109(6): 454-457. doi:10.1016/j.anai.2012.08.014


Image source: Wikipedia, GNU Free Documentation License.


Inhaled corticosteroids at high doses appear to be a significant independent risk factor for adrenal insufficiency

Adrenal insufficiency is a potential complication of therapy with inhaled corticosteroids (ICS). Previous studies found the highest risk of adrenal insufficiency with fluticasone. This study reexamined the relationship between the use of ICS and adrenal insufficiency by using a cohort of patients treated for respiratory conditions during 1990-2005 in Quebec, Canada, with follow-up until 2007.

Cases of adrenal insufficiency were matched with up to 10 controls. 392 cases were identified (incidence rate=1/10,000 person-years). The rate of adrenal insufficiency was not significantly higher among all current users of ICS. However, patients receiving the highest dosages showed a greater risk (OR=1.84).

Inhaled corticosteroids at high doses appear to be a significant independent risk factor for adrenal insufficiency. Physicians prescribing ICS at higher doses should be aware of the signs and symptoms of adrenal insufficiency in their patients.


Lapi F, Kezouh A, Suissa S, Ernst P. The use of inhaled corticosteroids and the risk of adrenal insufficiency. European Respiratory Journal 2012; Published online before print 11 October; erj00809-2012. doi:10.1183/09031936.00080912



68% of caregivers incorrectly treat children's asthma exacerbation with albuterol, most undertreat

Increased asthma morbidity and mortality is associated with inappropriate home self-management skills. This study included caregivers of 84 children with asthma aged 4 to 14 years, presenting to the emergency department (ED) with an asthma exacerbation. National Asthma Education and Prevention Program guidelines were used to classify home albuterol use as appropriate or inappropriate.

Home albuterol use for the current asthma exacerbation was categorized as:

  • inappropriate in 68% of participants
  • appropriate in 32%

Incorrect home albuterol use included:

  • undertreating, including not giving albuterol frequently enough, and without albuterol at home.
  • no spacer
  • overtreating
  • overreacting
  • using a controller medicine for quick relief

Those with appropriate albuterol use were more likely to have their child hospitalized for asthma in the past 48 months.

A significant proportion of caregivers (68%) incorrectly treat children's asthma exacerbation with albuterol. Correctly assessing asthma symptom severity and appropriate home albuterol use may be linked to disease experience such as previous hospitalizations.


Clayton K, Monroe K, Magruder T, King W, Harrington K. Inappropriate home albuterol use during an acute asthma exacerbation.  Annals of Allergy Asthma and Immunology 2012; 109(6): 416-419. doi:10.1016/j.anai.2012.09.013.


Last updated: Thursday, May 14th, 2015