Editorial August 1997 Asmanet The use of induced sputum to follow asthmatics in the clinical practice

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màj : 21/07/98

EDITORIAL FOR ASMANET
August 1997

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The use of induced sputum to follow asthmatics
in the clinical practice

Prof. José Roberto Lapa e Silva, M.D., Ph.D.
Professor of Pulmonary Medicine
HUCFF - Federal University of Rio de Janeiro, Brazil

Asthma is well recognized as a major Public Health problem. Despite the enormous strides over the last few years towards unraveling the mechanisms that lead to the disease and the development of novel drugs, all the major epidemiological parameters of the disorder experienced deterioration worldwide (9). The last 10 years witnessed an impressive change in the concept of the disorder. The advent of safe endoscopic methods allowed the study of the bronchial mucosa during the natural history of the disease, and it became clear that chronic bronchial inflammation underlies all types of asthma, including the mild forms of the disease (7). The inflammation is multifactorial and involves a great number of cells and mediators. This led to a redefinition of the disease and the proposal of new pharmacological approaches. An attempt to establish firm guidelines for asthma management worldwide resulted in the GLOBAL INITIATIVE FOR ASTHMA 1995 (9). It is now widely accepted that asthma is a chronic inflammatory disease of the airways but little change has emerged from the use of this concept as far as diagnosis and management of the asthmatic patients are concerned. In other words, there is a great gap between scientific knowledge and clinical practice. Despite the enormous advances in understanding the nature and role of bronchial inflammation in all forms of asthma, this knowledge has not being translated into new diagnostic and monitoring tools in the clinical setting. The gap in part derives from the fact that the endoscopic methods used to change completely the concept of the disorder are invasive, expensive, and not readily available.

This led the GLOBAL INITIATIVE FOR ASTHMA 1995 to propose a research recommendation: "To develop reliable, preferably non-invasive tests to reflect the asthmatic airway inflammation for use in diagnosis, monitoring the activity of the disorder, and evaluation of treatment" (9). Over the last few years, an old method that was mainly used in the past for bacteriologic diagnosis of tuberculosis was re-introduced in the clinical practice to allow a quick, non-invasive diagnosis of opportunistic infections in AIDS patients (2), the induction of sputum production by ultrasonic nebulization of hypertonic saline. Since the beginning of this decade, the method was adopted by some researchers for the study of asthma inflammation (3-6,8,10).

So, induced sputum could possibly "bridge the gap" alluded before. Induced sputum is a safe, reliable, non-invasive, and cost-effective way of exploring airway inflammation in asthma and can be repeated at regular intervals (11). It has been used by several groups to answer specific questions in asthma and over 100 publications appeared on leading journals on the last two years. A clear upward trend in research on the subject could be seen at the American Thoracic Society International Meetings: the numbers of free communications dealing with asthma and induced sputum in 1991 were six, in 1993 four, in 1995 twenty-six and in 1997 forty. The large critical mass of information accrued on the use of induced sputum in asthma can now be safely used for what is still missing: its use in the clinical setting "for diagnosis, monitoring the activity of the disorder, and evaluation of treatment", as suggested by GINA.

Asthma is a complex syndrome characterized by variability over time and its management can be different from one clinician to another and from one country to another (1). The assessment of severity appears to be a milestone of good therapeutic decision. However, even if the treatments are effective on a short term basis, we have no clear idea of the evolution of the disease with a treatment adapted to changes in severity. So there is a need for clarifying the concept of severity of asthma, looking for predictive factors of the outcome, with the help of inflammatory markers. Exacerbation represents one of the major outcomes in asthma, in terms of clinical evaluation but also in terms of cost for the society. New research is needed in order to establish which markers of bronchial inflammation can predict this outcome. It will be necessary to validate these markers on a prospective study, with the help of induced sputum.

...

2- Bigby TD, Margolskee D, Michael PF, Sheppard D, Hadley WK, Hopewell PC. The usefulness of induced sputum in the diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunedeficiency syndrome. Am. Rev. Respir. Dis. 1986; 113:515-518.

9- National Institutes of Health/National, Heart, Lung, and Blood Institute/World Health Organization.Global Initiative for Asthma. National Institutes of Health/National, Heart, Lung, and Blood Institute Publication Number 95-3659, January 1995.

Abstract 01 Heterogeneity of bronchial asthma. Sub-populations--or different stages of the disease.

Abstract 02 :The usefulness of induced sputum in the diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome.
Author : Bigby TD; Margolskee D; Curtis JL; Michael PF; Sheppard D; Hadley WK; Hopewell PC

Source : Am Rev Respir Dis, 133(4):515-8 1986 Apr
Abstract :
Thirty-two patients with or suspected of having the acquired immunodeficiency syndrome were
evaluated for opportunistic lung infection using examination of sputum induced by inhalation of 3%
saline. The specimens obtained were stained with Giemsa stain and examined for Pneumocystis carinii. Smears of sputum were also appropriately stained and examined for acid-fast organisms and fungi, as well as cultured for these organisms. Patients whose sputum did not contain P. carinii had bronchoscopy within 24 h of sputum induction. Twenty-five of the 32 patients were ultimately determined to have P. carinii pneumonia. Of these, ......

Abstract 03 :Cellular and biochemical analysis of induced sputum from asthmatic and from healthy subjects.
Author: Fahy JV; Liu J; Wong H; Boushey HA
Address : Department of Medicine, University of California, San Francisco 94143.
Source : Am Rev Respir Dis, 147(5):1126-31 1993 May

Abstract
To determine the feasibility of cellular and biochemical analysis of sputum induced after inhalation of
hypertonic (3%) saline, we analyzed sputum induced in 10 healthy and in 18 asthmatic subjects. We also analyzed saliva samples from all subjects. The entire sputum sample and the saliva sample were reduced using dithiothreitol, and cell counts and differentials were determined. Biochemical analysis was performed on sputum and saliva supernatants obtained after centrifugation. We found that induced sputum from asthmatic subjects had a higher percentage of ...

Abstract 04 : Comparison of samples collected by sputum induction and bronchoscopy from asthmatic and healthy subjects.
Author : Fahy JV; Wong H; Liu J; Boushey HA
Address : Department of Medicine, University of California, San Francisco 94143, USA.
Source : Am J Respir Crit Care Med, 152(1):53-8 1995 Jul

Abstract
To compare markers of inflammation in secretions obtained by sputum induction (SI), bronchial wash (50 ml instillate ÍBWÍ), and bronchoalveolar lavage (4 x 60 ml instillates ÍBALÍ), we analyzed markers of inflammation in samples obtained by these methods in 10 healthy and 10 asthmatic subjects. Of the asthmatic subjects 8 had mild disease (FEV1, % of predicted > 75%). Within subjects from both groups, we found that sputum, compared with either BW or BAL, had higher numbers of nonsquamous cells (p = 0.0001) and higher levels of eosinophil cationic protein (ECP) ...

Abstract 05 : Cellular characteristics of sputum from patients with asthma and chronic bronchitis.
Author : Gibson PG; Girgis-Gabardo A; Morris MM; Mattoli S; Kay JM; Dolovich J; Denburg J; Hargreave FE
Address : Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Source : Thorax, 44(9):693-9 1989 Sep

Abstract
The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but ...

Abstract 06 : Sputum measurements to assess airway inflammation in asthma.
Author : Hargreave FE; Popov T; Kidney J; Dolovich J
Address : Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Source : Allergy, 48(17 Suppl):81-3; discussion 84-6 1993
Language Eng

Abstract 07 :Asthma and inflammation.
Author : Kay AB
Address : Department of Allergy and Clinical Immunology, National Heart & Lung Institute, London, England.
Source : J Allergy Clin Immunol, 87(5):893-910 1991 May
Language : Eng

Abstract 08 : Sputum eosinophilia after asthmatic responses induced by isocyanates in sensitized subjects.
Author : Maestrelli P; Calcagni PG; Saetta M; Di Stefano A; Hosselet JJ; Santonastaso A; Fabbri LM; Mapp CE
Address : Institute of Occupational Medicine, University of Padova, Italy.
Source : Clin Exp Allergy, 24(1):29-34 1994 Jan

Abstract
To assess the nature and the time-course of the cellular component of airway inflammation induced by isocyanates, we examined nine subjects with occupational asthma induced by toluene- or methylene diphenyl-diisocyanate (TDI, MDI) and four control subjects never exposed to isocyanates. Sputum was induced by inhalation of ultrasonically nebulized hypertonic saline (3-4% NaCl) before and 8, 24, 48 h after inhalation challenge with TDI or MDI. Expectorated samples were incubated with dithiothreitol, washed and cytocentrifuged. Differential cell counts were obtained on slides stained with May-GrÍunwald-Giemsa. Metachromatic cells (mast cells and basophils) were counted on ...

Abstract 10 : Use of induced sputum cell counts to investigate airway inflammation in asthma.
Author : Pin I; Gibson PG; Kolendowicz R; Girgis-Gabardo A; Denburg JA; Hargreave FE; Dolovich J
Address : Department of Medicine, St Joseph's Hospital, Hamilton, Ontario, Canada.
Source : Thorax, 47(1):25-9 1992 Jan

Abstract
BACKGROUND: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. METHODS: A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to ...

Abstract 11 : Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.
Author : Pizzichini E; Pizzichini MM; Efthimiadis A; Evans S; Morris MM; Squillace D; Gleich GJ; Dolovich J; Hargreave FE
Address : Department of Medicine, St. Joseph's Hospital, Hamilton, Ontario, Canada.
Source : Am J Respir Crit Care Med, 154(2 Pt 1):308-17 1996 Aug

Abstract
Methods to examine sputum for indices of airway inflammation are evolving. We have examined the repeatability and the validity of an improved method to measure sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen, tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers with nonobstructive bronchitis. The method included the processing of freshly expectorated sputum separated from saliva, treatment with a fixed proportion of dithiothreitol 0.1% followed by Dulbecco's phosphate-buffered saline, making cytospins, and collecting the supernatant. The reproducibility of measurements, ...

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Date de création: Aout 97 - Dernière mise à jour: 21/07/98
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