Non-invasive Evaluation of Airway Inflammation in Asthma - What Has Been Learnt from Induced Sputum?
Non-invasive Evaluation of Airway Inflammation in Asthma - What Has Been Learnt from Induced Sputum?
Published: October 2008
Reference Section a report by Catherine Lemiýre, MD, MSc Department of Chest Medicine, Sacrý-Coeur Hospital Introduction One of the main characteristics of asthma is airway inflammation.The assessment of airway inflammation is most important in asthma since it reflects the disease directly, as opposed to spirometry and airway responsiveness, which are indirect functional markers of the condition. Several methods, such as bronchial biopsies, bronchoalveolar lavage (BAL), and induced sputum, make it possible to assess airway inflammation.
Bronchial biopsies and BAL, however, are too invasive to be used on a routine or serial basis.
Analyzing induced sputum is a reproducible, valid, responsive, and non-invasive method for studying airway inflammation. This method consists of inducing sputum production by inhalation of a hypertonic saline solution.The reproducibility of this method has been clearly demonstrated for differential cell counts performed within six days in healthy subjects, asthmatics and smokers ý the intraclass correlation coefficient for sputum eosinophils was high (0.94).1 The validity of the inflammation markers has been assessed by comparing cellular and fluid-phase components of healthy subjects with those of asthmatics and smokers with non- obstructive bronchitis. In comparison with healthy subjects, asthmatics had an increase in eosinophils, metachromatic cells and neutrophils, and of eosinophilic cationic protein (ECP), tryptase, albumin fibrinogen, and interleukin (IL)-5. The responsiveness of sputum examination has been demonstrated in situations where airway inflammation has been induced or treated.
Eosinophils and ECP concentrations are increased by exposure to common2ý5 or occupational6 allergens and reduction of steroid treatment.7 In contrast, they are decreased by treatment with corticosteroids.8,9 There is no difference in cell counts between spontaneous and induced sputum except that the viability of induced sputum is higher than that of spontaneous sputum.10Induced sputum is extensively used in research, but several papers have recently shown its interest in clinical practice.
Sputum Eosinophil Counts as a Predictor of the Response to Corticosteroids in Asthma and Chronic Obstructive Pulmonary Disease Some studies suggest that the presence of sputum eosinophilia may be a good predictor of response to inhaled steroids in asthmatic subjects. Pavord et al.11 showed that steroid-naýve asthmatic subjects who had a sputum eosinophilia equal to or greater than 3% had a better response to treatment with inhaled steroids thansubjects with sputum eosinophils lower than 3%.
Godon et al.12 found that subjects with eosinophilslower than 1% also had a satisfactory response to inhaled steroid treatment, but the improvement of forced expiratory volume in one second (FEV1) after treatment was inversely correlated with the reduction of sputum eosinophils. Furthermore, the subjects whose FEV1 improved the most after treatment those who had a higher eosinophil count.
Similarly,in subjects with chronic obstrutive pulmonary disease (COPD), sputum eosinophilia seems to be a predictor of a better response to corticosteroids. Indeed, Pizzichini et al.13 showed that subjects with COPD who showed a sputum eosnophilia equal to or higher than 3% had a significant improvement in FEV1 after treatment with oral prednisone, in contrast with those who had sputum eosinophilia lower than 3%.
Furthermore, Brightling et al.14 showed that among 67 subjects with COPD, only the subjects with sputum eosinophilia higher than 4% had a significant increase in postbronchodilator FEV1, quality of life, and shuttle walk distance after treatment with prednisolone.
Use of Sputum Cell Count as a Tool to Improve the Management of Asthma The association between a good response to inhaled steroids and the presence of sputum eosinophilia suggests that it may be interesting to target the reduction of eosinophilic airway inflammation as an important outcome in the management of asthma.
Green at al.15 randomized 74 mild-to-moderate asthmatics into two groups of asthma management, Non-invasive Evaluation of Airway Inflammation in Asthma ý What Has Been Learnt from Induced Sputum? 1 B USINESS BRIEFING: US RESPIRATORY CARE 2005 Catherine Lemiýre, MD, MSc, is a Respirologist at Sacrý-Coeur Hospital in Montreal, Quebec, Canada. She is an Associate Professor at the University of Montreal. She graduated from the University of Aix-Marseille, France, as a Respirologist in 1994. Dr Lemiýre completed her training by performing two successive fellowships at the University of Montreal, working in the field of occupational asthma, and at McMaster University, working on a non-invasive method of assessing airway inflammation ý induced sputum. Her main research interest is the investigation of the pathophysiology of occupationalasthma.
- Pizzichini E, Pizzichini M, Efthimiadis A, Evans S, Morris M, Squillace D et al.,-Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements-, Am. J. Respir. Crit. Care Med. (1996), 154: pp. 308-317.
- . Pin I, Freitag A, O-Byrne P, Girgis-Gavardo A,Watson R, Dolovich J et al.,-Changes in the cellular profile of induced plutum after allergen- induced asthmatic responses-, Am. Rev. Respir. Dis. (1992), 145: pp. 1,265-1,269.
- Fahy J, Liu J,Wong H, Boushey H,-Analysis of cellular and biochemical constituents of induced sputum after allergen challenge: A method for studying allergic airway inflammation-, J. Allergy Clin. Immunol. (1994), 93: pp. 1,031-1,039.
- Wong B, Dolovich J, Ramsdale E, O-Byrne P, Gontovnick L, Denberg J et al.,-Formoterol compared with beclomathasone and placebo on allergen- induced asthmatic responses-, Am. Rev. Respir. Dis. (1992), 146: pp. 1,156-1,160.
- Pizzichini M, Kidney J,Wong B, Morris M, Efthimiadis A, Dolovich J et al.,-Effect of salmeterol compared with beclomethasone on allergen- induced asthmatic and inflammatory responses-, Eur. Respir. J. (1996), 9: pp. 449-455.
- Maestrelli P, Calcagni P, Saetta M, Stefano A D, Hosselet J, Santonastaso A et al.,-Sputum eosinophilia after asthmatic responses induced by isocyanates in sensitized subjects-, Clin. Exp.Allergy (1994), 24: pp. 29-34.
- Gibson P,Wong B, Hepperle M, Kline P, Girgis-Gavardo A, Guyatt G et al.,-A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid-, Clin. Exper.Allergy (1992), 22: pp. 525-532.
- Gibson P, Hargreave F, Girgis-Gabardo A, Morris M, Denburg J, Dolovich J, -Chronic cough with eosinophilic bronchitis: examination for variable airflow obstruction and response to corticosteroid-, Clin. Exp.Allergy (1995), 25: pp. 127-132.
- Pizzichini M M, Pizzichini E, Clelland L, Efthimiadis A, Mahony J, Dolovich J et al., -Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment-, Am. J. Respir. Crit. Care Med. (1997), 155 (5): pp.
1,501-1,508.
- Pizzichini M, Popov T, Efthimiadis A, Hussack P, Pizzichini S E E, Dolovich J et al.,-Spontaneous and induced sputum to measure indices of airway inflammation in asthma-, Am. J. Respir. Crit. Care Med. (1996), 154: pp. 866-869.
- Pavord I D, Brightling C E,Woltmann G,Wardlaw A J,-Non-eosinophilic corticosteroid unresponsive asthma [letter]-, Lancet (1999), 353 (9171): pp. 2,213-2,214.
- Godon P, Boulet L P, Malo J L, Cartier A, Lemiere C, -Assessment and evaluation of symptomatic steroid-naive asthmatics without sputum eosinophilia and their response to inhaled corticosteroids-, Eur. Respir. J. (2002), 20 (6): pp. 1,364-1,369.
- Pizzichini E, Pizzichini M M, Gibson P, Parameswaran K, Gleich G J, Berman L et al.,-Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis-, Am. J. Respir. Crit. Care Med. (1998), 158 (5 Pt 1): pp.
1,511-1,517.
- Brightling C E, Monteiro W,Ward R, Parker D, Morgan M D,Wardlaw A J et al.,-Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial-, Lancet (2000), 356 (9240): pp.
1,480-1,485.
- Green R H, Brightling C E, McKenna S, Hargadon B, Parker D, Bradding P et al., -Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial-, Lancet (2002), 360 (9347): pp. 1,715-1,721.
- Lemiere C, Pizzichini M M, Balkissoon R, Clelland L, Efthimiadis A, O-Shaughnessy D et al., -Diagnosing occupational asthma: use of induced sputum [see comments]-, Eur. Respir. J. (1999), 13 (3): pp. 482-488.
- Anees W, Huggins V, Pavord I D, Robertson A S, Burge P S, -Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants-, Thorax (2002), 57 (3): pp. 231-236.
- Leigh R, Hargreave F E,-Occupational neutrophilic asthma-, Can. Respir. J. (1999), 1999 Mar-Apr;6 (2): pp. 194-196.
Non-invasive Evaluation of Airway Inflammation in Asthma BUSINESS BRIEFING: US RESPIRATORY CARE 2005 4
- Girard F, Chaboillez S, Cartier A, Cote J, Hargreave F E, Labrecque M et al.,-An Effective Strategy for Diagnosing Occupational Asthma: Use of Induced Sputum-, Am. J. Respir. Crit. Care Med. (2004).
- Gibson P, Dolovich J, Denburg J, Ramsdale E,-Chronic cough: eosinophilic bronchitis without asthma-, Lancet (1989), 334: pp. 1,346-1,348.
- Brightling C E,Ward R, Goh K L,Wardlaw A J, Pavord I D,-Eosinophilic bronchitis is an important cause of chronic cough-, Am. J. Respir. Crit. Care Med. (1999), 160 (2): pp. 406-410.
- Lemiere C, Efthimiadis A, Hargreave F E,-Occupational eosinophilic bronchitis without asthma: an unknown occupational airway disease-, J. Allergy Clin. Immunol. (1997), 100 (6 Pt 1): pp. 852-853.
- Quirce S, Fernandez-Nieto M, de Miguel J, Sastre J,-Chronic cough due to latex-induced eosinophilic bronchitis-, J. Allergy Clin. Immunol. (2001), 108 (1): p. 143.
Specialities:
- 22 August 2010
- 2 September 2010
- 12 September 2010







add new comment Comments