Chronic cough and phlegm in young adults

The enormous cost of chronic obstructive pulmonary disease (COPD) and its increase over the foreseeable future are constant reminders that the disease is not adequately managed 1, 2. In previous years strong epidemiological evidence has shown chronic cough and phlegm production are significantly related to COPD death 3–5, excess FEV₁ decline 6, 7, and increased risk of subsequent hospitalisation because of COPD 6. This information overturned the beliefs, based on classical epidemiological studies conducted in the 1960s, that mucus hypersecretion and airflow obstruction are largely independent disease processes 8, 9. The recently published guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) underline that the presence of chronic cough and sputum production before airflow obstruction offers a unique opportunity to identify subjects at risk for COPD (GOLD stage 0) for an early intervention 10. In a recent study Vestbo and Lange 11 tried to validate this staging approach, retrospectively, using data from three surveys in the Copenhagen City Heart Study. This study examined a sample taken from the general population, at baseline and after 5 and 15 yrs, by taking spirometric readings at each stage. The authors concluded that GOLD stage 0 is of little help in identifying subjects at risk for COPD. This statement is a key point that requires further investigation as it could profoundly influence future strategies for the early detection and prevention of COPD 12.

Current epidemiological data on subjects with chronic cough and phlegm are scant. Rapid changes in environmental, behavioural (particularly smoking habits) and socioeconomic conditions in the last few decades throughout the world 13, mean that ad hoc population-based studies are needed 14. The Italian Study on Asthma in Young Adults (ISAYA) provided the present authors the opportunity to assess the prevalence of subjects with chronic cough and phlegm in the youngest age classes and to evaluate these subjects' main characteristics and risk factors.

Methods

Results

The overall prevalence of subjects with chronic cough and phlegm was 11.9% (95% CI: 11.4–12.4), of which the prevalence of subjects with chronic cough and phlegm without coexisting asthma was 9.5% (9.1–10) and the prevalence of those with coexisting asthma was 2.2% (2.0–2.4). The prevalence was not significantly different between males and females either in the whole group of subjects with chronic cough and phlegm or in those with and without coexisting asthma (table 1⇓).

The prevalence of current smokers was 33.3% (32.5–34.0) and varied significantly according to sex: 37.1% (36.1–38.1) in males and 29.9% (29–30.8) in females (p<0.001). The prevalence of past smokers was 13.1% (12.6–13.6), 13.9% (13.2–14.6) in males and 12.4% (11.7–13.1) in females (p=0.001). The median (95% CI) number of pack-yrs was significantly higher among males than among females 10.2 (9.7–10.6) versus 7.5 (7.0–7.8) pack-yrs (p<0.001) and, on average, males started smoking significantly earlier than females (p<0.001). According to the authors classification, the percentage of moderate-heavy smokers was higher in males than in females (33.1% versus 22.9%; p<0.001).

Subjects with chronic cough and phlegm included a larger proportion of current smokers (53.5% versus 30.7%, p<0.001), in particular moderate-heavy smokers (22.4% versus 7.7%), than those without chronic cough and phlegm. The prevalence of subjects with chronic cough and phlegm progressively increased from among nonsmokers to among moderate-heavy smokers (fig. 1⇓) and from among people of the higher socioeconomic classes to among the unemployed and workers (fig. 2⇓). About 30% of subjects with chronic cough and phlegm were nonsmokers. In comparison with current smokers, they were significantly younger, there were significantly more females, and more subjects with coexisting asthma and nasal allergies. The socioeconomic status of this subgroup was also different, as it contained more housewives and fewer workers (table 2⇓).

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Fig. 1.—

Prevalence (95% confidence interval) of chronic cough and phlegm plotted by sex (□: males; ┘: females) and smoking habits. The prevalence is adjusted for age, cumulative response rate and type of contact (telephone versus mail).

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Fig. 2.—

Prevalence (95% confidence interval) of chronic cough and phlegm plotted by sex (□: males; ┘: females) and socioeconomic status. Adjusted for age, cumulative response rate and type of contact (telephone versus mail).

From the total of 2,318 subjects with chronic cough and phlegm, 455 (19.8%) (204 males and 251 females) reported coexisting asthma. These subjects were significantly younger than subjects reporting only chronic cough and phlegm (31.9 versus 33.4 yrs, p<0.001), and more often reported wheezing (71.0% versus 29.4%, p<0.001) and nasal allergies (64.1% versus 31.1%, p<0.001). Moreover, these subjects were characterised by a significantly lower percentage of current smokers (40.5% versus 56.7%, p<0.001) and a lower cumulative consumption of cigarettes (8.4 versus 13.4 pack-yrs) than subjects reporting only chronic cough and phlegm. Anyway, the percentage of current smokers in subjects with chronic cough and phlegm with coexisting asthma was higher than that of the population as a whole.

Table 3⇓ shows the adjusted ORs for the association between the presence of chronic cough and phlegm and sex, smoking habit and socioeconomic status for subjects with chronic cough and phlegm divided according to whether or not they also had asthma. All the three factors were significantly and independently associated with chronic cough and phlegm in both groups. The effect of smoking habits was much less evident in those with coexisting asthma, and not apparently related to the number of cigarettes smoked.

Discussion

The prevalence of subjects with chronic cough and phlegm is startlingly high among young adults without difference between sex. Alongside smoking, which is already well known for playing a major role, sex and low socioeconomic status were significantly and independently associated with chronic cough and phlegm. Even considering chronic respiratory symptoms in many of these subjects may be reversible or attributable to diseases not resulting in COPD, this data suggests how large the bottom of the COPD iceberg is.

Estimates in past decades showed chronic cough and phlegm were more prevalent among males than females, a finding attributed to higher smoking rates and more frequent occupational exposure for males 21, 22. According to other studies 13, 23, 24, particularly those with data collected more recently, the authors found that the prevalence of chronic cough and phlegm among females has already reached that among males and that to be female has an effect on chronic cough and phlegm independently from smoking. Even if studies of a sex-related effect of smoking on respiratory outcomes have not been conclusive, there is increasing evidence of a higher prevalence of smoking and long-term cumulative effect of smoking among women after the 1970s. Some studies had suggested a possibly greater susceptibility to the adverse pulmonary effects of smoking 13, 25. However, it is difficult to control for all the circumstances of exposure and the effects of smoking in females could be underestimated, since males not only smoke more than females, but they have often started earlier as observed in the present study and have a higher rate of inhalation than females 26.

Although smoking was the major risk factor, the authors observed that a considerable proportion of symptomatic subjects were nonsmokers. These subjects were predominantly females, and frequently reported coexisting asthma and nasal allergies. Epidemiological studies have already shown that 5–12% of patients with a diagnosis of COPD have never smoked and there is evidence of an increasing incidence with increasing age 27; these subjects were predominantly females and there was an association with lower income 28. Therefore it should be considered that, at least in some of the subjects with chronic cough and phlegm, particularly the nonsmokers, a different pathogenesis such as asthma, chronic rhinosinusitis or gastroesophageal reflux could be involved. These patients could have a different disease evolution and may not go on to develop bronchial obstruction in the future, particularly if properly diagnosed and treated.

In the present study sample, 20% of subjects with chronic cough and phlegm also reported asthma. It is well recognised that there is an overlap between asthma and COPD in some patients but it cannot be excluded that chronic cough and phlegm are purely expressions of asthma. The earlier onset of symptoms in these patients, the association with nasal allergies, as a marker of atopy, wheezing and the minor role of current smoking in these subjects seem to suggest that many of them have only asthma.

Even if only some of the subjects with chronic cough and phlegm will go on to develop chronic airflow obstruction, all subjects with chronic cough and phlegm should be carefully evaluated, presumably mainly in the primary care context but in any setting that they are first recognised. The GOLD guidelines stated that spirometry should be undertaken for any patients who have chronic cough and sputum production even if they do not have dyspnoea. All the moderate-heavy smokers should also undergo spirometry because they could be more motivated to stop smoking if they realise that their respiratory problems are caused by smoking and that they are at risk of developing COPD 29. Smoking cessation has been proven to be capable of reversing the steep decline in lung function 30 and, at present, it is the only intervention able to do so. Recent results of the Lung Health Study showed that males and females who quit smoking at the beginning of the study and were still abstaining after 11 yrs had almost halved the decline of FEV₁ per year as compared to those who continued to smoke throughout the 11 yrs. At 11 yrs, 38% of individuals who continued to smoke had a FEV₁ <60% of the predicted normal value, as compared with 10% in the individuals who stopped smoking permanently. Anthonisen et al 31 concluded that the loss of lung function among continuing smokers is more rapid than previously suspected. It is particularly important to study young adults, as the present authors did, because there is evidence suggesting that the benefits of smoking cessation are greatest at younger ages, usually before 45 yrs 32.

In a recent study Vestbo and Lange 11 raised an important point, showing that chronic cough and phlegm are not stable features since, in their retrospective study, ∼40% of subjects who reported chronic respiratory symptoms no longer did so after 5 yrs. Smoking cessation was found to predict the subsequent absence of chronic symptoms. The present authors' interpretation on finding that disappearance of chronic mucus hypersecretion is associated with young age and smoking cessation differs from that of Vestbo and Lange 11 as it indicates the opportunity for early detection of these subjects in order to promote smoking cessation 12.

The strengths of this present epidemiological study are its large sample size, robust study design and statistical analysis. In particular, differently from other studies, the present study sample was selected from young adults, allowing the authors to estimate how large the bottom of the COPD iceberg is; in fact, during the course of such a chronic disease, patients are supposed to move from low stages upwards.

The limitations of this present study are the use of a simple screening questionnaire that does not allow deep investigation on the specific characteristics of the subjects and the absence of spirometry. In the authors' previous international study, which focused on subjects of the same age range, the prevalence of airflow obstruction in young adults with chronic cough and phlegm was only 8.4% 33.

In conclusion, the impressively high prevalence of subjects with chronic cough and phlegm among young adults, although only some of them will develop chronic obstructive pulmonary disease, supports the projections of a remarkable increase of chronic obstructive pulmonary disease over the foreseeable future. The final message is that subjects with chronic cough and phlegm should be carefully evaluated in the primary care context or in any other setting as soon as these symptoms are first recognised and should have access to spirometry. Unfortunately, the present cross-sectional study does not answer the inevitable question surrounding the progression from cough and sputum to airflow obstruction or indeed whether intervention can prevent the inevitable. Prospective population-based studies are needed, particularly in the youngest age ranges, to validate the predictive value of chronic cough and phlegm in the development of chronic obstructive pulmonary disease.