Treatment of Chronic Asthma With Prednisolone Significance of Eosinophils in the Sputum

Brown, H. Morrow

doi:10.1016/s0140-6736(58)91385-0

Cited by 186 publications

(40 citation statements)

References 6 publications

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“…We have known for over 50 years that patients with asthma and sputum eosinophilia responded to steroid treatment, which was elegantly demonstrated by Dr Harry Morrow Brown after a negative clinical trial of corticosteroids in “all-comers” with asthma [22]. Despite this initial foray into personalised medicine, it has taken us many years to consider moving away from using excessive doses of steroids in patients with airways disease.…”

Section: Understanding the Clinical Problem - A Personal Issuementioning

confidence: 99%

Personalised Medicine for Asthma and Chronic Obstructive Pulmonary Disease

Heaney

McGarvey²

2017

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Asthma and chronic obstructive pulmonary disease (COPD) are prevalent conditions, and despite recent advances and multiple available therapies and interventions, there remains a significant unmet clinical need. In recent years, it has become clear that there is both significant heterogeneity within each of these conditions and additionally significant overlap in many of the clinical and inflammatory features. In parallel, useful clinical and immunological biomarkers which inform about prognosis and response to therapy have emerged in both asthma and COPD. These biomarkers will allow both better targeting of existing treatments and the identification of those patients who will respond to novel therapies which are now becoming available. Biomarkers will also facilitate the identification of novel therapeutic targets for future development. Delivery of precision medicine in airways disease is now feasible and is a core component of a personalised healthcare delivery in asthma and COPD.

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Section: Understanding the Clinical Problem - A Personal Issuementioning

confidence: 99%

Personalised Medicine for Asthma and Chronic Obstructive Pulmonary Disease

Heaney

McGarvey²

2017

Respiration

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“…He observed marked symptomatic improvement in 57, partial response in 10, and no benefit in the remaining 23 patients. 4 A plausible explanation was that he was treating 2 different diseases characterized by corticosteroid responsiveness and nonresponsiveness. He focused on the presence of eosinophils in the sputum as a possible differentiating factor to discover that 63 of 67 patients who responded to prednisolone had many eosinophils, whereas those who did not respond to treatment had none.…”

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confidence: 99%

“…He focused on the presence of eosinophils in the sputum as a possible differentiating factor to discover that 63 of 67 patients who responded to prednisolone had many eosinophils, whereas those who did not respond to treatment had none. 4 Abbreviations used CDHR3: Cadherin-related family member 3 CRD: Component-resolved diagnostics FENO: Fraction of exhaled nitric oxide ICS: Inhaled corticosteroid INFANT: Individualized Therapy for Asthma in Toddlers LABA: Long-acting b 2 -agonist LRTA: Leukotriene receptor antagonist RCT: Randomized controlled trial UK: United Kingdom His observations were remarkable, even by today's standards: (1) prednisolone is effective in the treatment of chronic asthma but only if the sputum contains large numbers of eosinophils;…”

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confidence: 99%

“…(2) if eosinophils are absent in the sputum, improvement is unlikely, and the use of corticosteroids might be contraindicated; and (3) although corticosteroids are effective in suitable cases, the treatment ''never does more than suppress the asthmatic state.'' 4 These extraordinary findings were published in 1958 but attracted little attention and were largely overlooked by most of the medical community at the time and in subsequent decades. This was the first example in asthmatic patients of using a biomarker for patient stratification to predict treatment response and is as relevant today as it was more than 6 decades ago.…”

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confidence: 99%

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Does understanding endotypes translate to better asthma management options for all?

Čustović

Henderson

Simpson

2019

Journal of Allergy and Clinical Immunology

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Despite the development of novel treatments, improvement in the design of delivery devices, and new technologies for monitoring and improving adherence, the burden of asthma is not decreasing. Predicting an individual patient's response to asthma drugs remains challenging, and the provision of personalized treatment remains elusive. Although biomarkers, such as allergic sensitization and blood eosinophilia, might be important predictors of response to inhaled corticosteroids in preschool children, these relatively cheap and available investigations are seldom used in clinical practice to select patients for corticosteroid prescription. However, for the majority of patients, response to different treatments cannot be accurately predicted. One of the key factors preventing further advances is the reductionist view of asthma as a single disease, which is forcing patients with different asthma subtypes into a single group for empiric treatment. This inevitably results in treatment failures and, for some, an unacceptable risk/benefit ratio. The approach to asthma today is an example of the traditional symptom (diagnosis)-based, onesize-fits-all approach rather than a stratified approach, and our guidelines-driven management based on a unitary diagnosis might not be the optimal way to deliver care. The only way to deliver stratified medicine and find a cure is through the understanding of asthma endotypes. We propose that the way to discover endotypes, biomarkers, and personalized treatments is through the iterative process based on interpretation of big data analytics from birth and patient cohorts, responses to treatments in randomized controlled trials, and in vitro mechanistic studies using human samples and experimental animal models, with technological and methodological advances at its core.

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“…Sputum analysis already opened perspectives to asthma phenotyping and customized therapy more than 50 years ago, when Dr Harry Morrow Brown from Derby, UK, started to treat symptomatic patients with sputum eosinophilia with corticosteroids [2]. In the 1990s, interest in sputum analysis revived when the late Dr Frederick Hargreave's research group in Hamilton, Ontario, Canada, introduced the technique of sputum induction by inhalation of hypertonic saline [3].…”

mentioning

confidence: 99%