Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids

Holme, Jayne; Tomlinson, Jeremy W.; Stockley, Robert A.; Stewart, Paul M.; Barlow, Nicola; Sullivan, Anita

doi:10.1183/09031936.00016908

Cited by 34 publications

(24 citation statements)

References 28 publications

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“…Holme et al identified a high frequency of adrenal suppression associated with ICS treatment in bronchiectasis. 176 A statistically significant increase in adverse effects was reported for high dose ICS in the trial of Martinez et al (P=0.04). 172 A trial of high dose budesonide vs budesonide with formoterol identified a numerical increase in the frequency of local side effects with high dose ICS (pharyngeal irritation, dysphonia and gingivitis) and a single case of pneumonia which is a recognised adverse effect of inhaled corticosteroid treatment in COPD.…”

Section: Sectionmentioning

confidence: 87%

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British Thoracic Society Guideline for bronchiectasis in adults

Hill

Sullivan

Chalmers

et al. 2018

Thorax

358

348

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Section: Sectionmentioning

confidence: 87%

“…176 Inhaled fluticasone treatment appeared to double the risk. Adrenal insufficiency was associated with poorer quality of life.…”

Section: Section 19mentioning

confidence: 99%

British Thoracic Society Guideline for bronchiectasis in adults

Hill

Sullivan

Chalmers

et al. 2018

Thorax

358

348

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“…Pre-and post-Synacthen total cortisol concentrations for the entire group, as measured in the original study, 12 …”

Section: Total Cortisol Concentrationsmentioning

confidence: 99%

An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Barlow¹,

Holme

Stockley

et al. 2010

Ann Clin Biochem

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Background: Since more than 90% of cortisol is bound to protein, serum free cortisol (SFC) may be a more appropriate marker of adrenal status than total cortisol. However, measurement of SFC is technically difficult and calculated SFC may offer a more practical alternative. Methods: SFC, measured by equilibrium dialysis coupled with immunoassay, and calculated using Coolens' equation from total cortisol and corticosteroid binding globulin (CBG) concentrations, was compared in short Synacthen test (SST) serum from 42 patients, of whom 20 demonstrated a suppressed adrenal response. Results: Considering the patient group as a whole, calculated SFC was found to be significantly lower than measured SFC, pre-and post-Synacthen (P , 0.05 and ,0.001, respectively). Upon classifying the patients as pass or fail based on total cortisol response to Synacthen, the difference in calculated and measured SFC only reached statistical significance for postSynacthen concentrations in the pass group (P , 0.01), suggesting a greater discrepancy at higher cortisol concentrations. There was no difference in CBG levels between the pass and fail groups and both measured and calculated SFC gave a diminished 30 min response in subjects deemed to have failed the SST. Conclusion: Coolens' equation was found to underestimate measured SFC in this cohort of outpatients, as has been previously demonstrated, particularly in patients with a pronounced acute phase response. Although calculated SFC gave a diminished response in individuals deemed to have failed the SST, the concentration-dependent nature of the discrepancy may limit the usefulness of this method for assessing adrenal status.

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“…In a small study of 5 PiZZ patients, Wilcke and Dirksen [33] have previously identified the potential benefit of ICS in improving lung function in patients with AATD-related emphysema. However, corticosteroid therapy carries a significant side effect burden, including oral thrush, adrenal suppression [34], and pneumonia [35,36]; hence indiscriminate use could cause harm without therapeutic benefit. Studies have previously shown that blood eosinophil count can be reliably used to direct oral corticosteroid therapy in exacerbations [13] and imply that reduced exacerbation rates are the key benefit for eosinophilic patients [15,16].…”

Section: Discussionmentioning

confidence: 99%

ICS Use May Modify FEV<sub>1</sub> Decline in α<sub>1</sub>-Antitrypsin Deficiency Patients with Relatively High Blood Eosinophils

Low

Hughes²,

Zaffarullah

et al. 2017

Respiration

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Background: α 1 -Antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease (COPD). In COPD unrelated to AATD, the role of a higher blood eosinophil count in disease and subsequent personalization of therapy has recently received much attention. We sought to investigate this concept in patients with AATD-associated COPD. Objectives: The study aims to evaluate eosinophilia status against outcomes including mortality and FEV 1 decline in patients with AATD. Methods: All patients with PiSZ and PiZZ genotypes were identified from the UK AATD registry. The participants were substratified according to inhaled corticosteroid (ICS) use. Blood eosinophil counts were assessed from baseline and annually during follow-up (range 1-18 years). Eosinophilia was defined as a level >0.2 × 10 9 /L, and classified by the frequency of such counts into "always," "intermittent," or "never present." Univariate and multivariate analyses were conducted. Results: In total, 646 participants were included, 53.9% of whom demonstrated intermittent and 7.4% persistent eosinophilia. Survival did not differ according to eosinophilic group (p > 0.05). Those with persistent eosinophilia showed a slower FEV 1 decline (p < 0.001). There was no clear association with exacerbation frequency. Patients on ICS at baseline were more likely to be eosinophilic (p = 0.002) and having a lower FEV 1 (p < 0.001) and greater pack-year exposure (16.5 vs. 7.8 pack-years, p < 0.001). When the multivariate analyses of FEV 1 decline were stratified for baseline ICS use, the association of persistent eosinophilia with slower decline persisted in those on ICS. Conclusions: Blood eosinophil levels persistently >0.2 × 10 9 /L may be an indication for ICS use in PiZZ AATD in order to reduce FEV 1 decline.

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Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids

Cited by 34 publications

References 28 publications

British Thoracic Society Guideline for bronchiectasis in adults

British Thoracic Society Guideline for bronchiectasis in adults

An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

ICS Use May Modify FEV<sub>1</sub> Decline in α<sub>1</sub>-Antitrypsin Deficiency Patients with Relatively High Blood Eosinophils

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