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During the last decade, the method of sputum induction (SI) has offered the opportunity to study inflammation in patients with chronic obstructive pulmonary disease (COPD). This paper reviews methodological aspects of SI and summarizes its uses in the research of inflammation in COPD, including sputum cellularity and soluble markers. SI is a relatively safe, reliable, and reproducible technique, used to investigate different aspects of airway inflammation. Although various methods of induction and processing have been proved safe and highly reproducible, a generally accepted method is needed. Sputum analysis has given evidence for increased numbers of macrophages and neutrophils in COPD patients compared to normal subjects. In some studies, increased numbers of eosinophils have been also reported. Changes in various mediators have been found in sputum supernatant of COPD patients (IL-8, LTB-4 and TNF-a). The clinical usefulness of the method in the follow-up of the disease has not been explored extensively. A number of observations in patients with different clinical characteristics could be proven useful in identifying patterns of inflammation associated with different prognosis. Finally, SI could also guide treatment; such as, sputum eosinophilia in COPD could predict response to inhaled corticosteroids.

This study aimed to determine whether there is a persistent or different type of airway inflammation in patients with an incomplete reversibility of airflow obstruction (IRAO) despite optimal treatment and if so, whether it is associated with an accelerated decline of pulmonary function. Fifteen asthmatic patients with IRAO, and 23 with complete reversibility of airflow obstruction (CRAO) had a spirometry and an induced-sputum (IS) analysis. Past FEV 1 values were recorded over 2–12 years during periods of stable asthma. Medians (range) for IS cell differentials were: lymphocytes, 0(0–3)/1(0–2)%; neutrophils, 56(13–88)/38(3–84)% and eosinophils, 2.0(0–82)/4.0(0–68)%, (all P >0.05). Among non-smoking patients, those with IRAO had more neutrophils in IS than those with CRAO ( P =0.019). Mean (±sem) yearly fall in FEV 1 in IRAO or CRAO patients was 54±21/84±16 ml/year ( P >0.05, predicted age-related decline ≤26ml/year, P =0.0008). In the whole group of asthmatic patients, decline of FEV 1 /year was inversely correlated with the % neutrophils in sputum ( r s =−0.436, P =0.008) and, in IRAO patients, with the duration of asthma ( r s =−0.559, P =0.037). In conclusion, persistent airway inflammation and increased decline in pulmonary function can be observed in both asthmatic patients with IRAO/CRAO and are of similar magnitude. Non-smoking patients with IRAO had more neutrophils in IS than CRAO.

The forced expiratory volume in 1 sec (FEV1) is the most established outcome measure in chronic obstructive pulmonary disease (COPD). However, changes in FEV1in response to treatment are small in relation to the repeatability of the measurement and there is increasing interest in other measures including markers of lower airway inflammation in induced sputum, assessment of symptoms and health status using visual analogue scores, and questionnaires. Little is known about the repeatability of these measures or the safety of sputum induction in COPD. We have assessed the safety of sputum induction in 61 subjects with moderate and severe COPD who participated in a placebo-controlled cross-over study. The within-subject repeatability of sputum markers of airway inflammation, health status using the chronic respiratory disease questionnaire (CRQ) and symptom visual analogue scores (VAS) were estimated from the data obtained from before and after 2 weeks of treatment with placebo. Sputum induction was performed on 122 occasions and was successful resulting in a cytospin adequate to assess a differential cell count in 95% of inductions. The group mean (SEM) FEV1was 1·09 (0·05)[41·6 (2·9)% predicted] and the mean (SEM) fall in FEV1after sputum induction was 120 ml (6) and % fall 10·9% (0·55%). Seven inductions were stopped due to a fall in FEV1>20% and at a further 13 visits the full sputum induction protocol was not completed due to development of symptoms. The reproducibility of measurements, calculated by the intra-class correlation coefficient, was relatively high for all indices measured (0·4–0·95) with the exception of the proportion of lymphocytes (0·15) and epithelial cells (0·3). The ICC for symptom scores and the CRQ domains ranged between 0·87 and 0·96. In conclusion, sputum induction is safe and the cell and fluid phase mediators repeatable in the investigation of airway inflammation in patients with COPD. VAS symptom scores and the CRQ are reproducible outcome measures in COPD.

SummaryIntroductionThe GOLD guidelines advocate not to institute inhaled corticosteroids (ICS) in patients with mild-to-moderate COPD. However, many patients do use ICS and in some patients, withdrawal is associated with deteriorating lung function and increased exacerbation rates. Unfortunately, physicians do not know in which patients they can stop ICS treatment safely.AimTo identify predictors of COPD exacerbations after ICS withdrawal.MethodsDuring ICS treatment, post-bronchodilator spirometry, body plethysmography, and health status assessment were performed in 68 COPD patients using ICS. Additionally, sputum cell differentials, supernatant leukotriene B4, eosinophilic cationic protein, and myeloperoxidase, serum C-reactive protein and soluble intracellular adhesion molecule, and urinary desmosine were assessed. Sputum was also analysed for mRNA levels of haemoxygenase-1, tumour necrosis factor-α, RANTES, interleukin 5(IL-5), IL-10, IL-12, IL-13, transforming growth factor-β, and interferon-γ.StatisticsCox regression analyses were performed using time to exacerbation as outcome variable to identify significant hazards for a COPD exacerbation after ICS withdrawal.ResultsHigher sputum % eosinophils, higher sputum MPO/neutrophil level, longer duration of COPD symptoms