Frequent cough in unsatisfactory controlled asthma – results from the population-based West Sweden Asthma Study

The grounds for the sample selection were based on a large scale population study, initiated in 2008 in West Sweden that is described in details elsewhere [5]. The sampling procedure is depicted on Figure 1. In short, an extensive postal questionnaire was sent to 30 000 people, randomly selected from the West Sweden region, aged 16-75 years, of which 18 087 participated. It comprised of the OLIN- questionnaire and a Swedish version of the GA²LEN questionnaire and additionally of questions about environmental and occupational exposures as well as family background and socioeconomic status. From the responders, a randomly selected sample of 2000 subjects as well as all those who reported ever asthma with current symptoms or asthma medication or physician diagnosed asthma (n = 1524) were invited to take part in the subsequent clinical phase of the study. Altogether, 2006 subjects agreed to participate in the clinical part which was conducted between 2009 and 2012.

The study was approved by the local Ethics Committee of University of Gothenburg.

Definitions are based on the questions from the interview:

Ever asthma:” Have you ever had asthma?”; Physician-diagnosed asthma:” Have you been diagnosed as having asthma by a doctor?”; Asthma medications:” Have you used asthma medications (permanently or as needed) in the last 12 months?”; Shortness of breath;”Have you ever had suddenly appearing shortness of breath or breathlessness?” and “have you had these symptoms in the last 12 months?”; Recurrent wheeze:” Do you usually have wheezing or whistling in the chest when breathing?”; Any wheeze:” Have you had whistling or wheezing in the chest on any occasion during the last 12 months?”; Wheezing with shortness of breath: Yes to Any wheeze and”Have you been at all breathless when the wheezing or whistling was present?”; Longstanding cough:” Have you had a longstanding cough during the last 12 months?”; Morning cough: “Do you usually cough or hawk in the mornings?”, Sputum production:” Do you usually cough or hawk phlegm from the chest, or do you feel like you have phlegm in the chest that is difficult to bring up by coughing and hawking?”; Sputum production longer than 3 months per year:” Do you cough of hawk phlegm (or do you have phlegm which is difficult to bring up despite coughing) most days in periods of at least 3 months per year?”; Allergic rhinitis:” Do you currently have or have you ever had allergic nose problems of hay fever?”; Physician – diagnosed COPD, chronic bronchitis, emphysema, tuberculosis:” Have you been diagnosed as having COPD, chronic bronchitis, emphysema or tuberculosis by a physician” (asked in separate questions); Doctor’s office visits:” Have you consulted a physician or other medical care because of breathlessness, shortness of breath or whistling in the chest, cough with or without phlegm, phlegm in the chest or other lung or airway problems in the last 12 months?”; Hospitalisations: “Have you been hospitalised due to problems with your breathing during the last 12 months?”; Emergency unit visits:” Have you visited the emergency unit because of problems with your breathing during the last 12 months?”; Level of asthma control – controlled, partly controlled and uncontrolled (according to GINA 2006 guidelines) based on the presence of daytime/nighttime symptoms, limitation of daily activities, use of reliever medications, pulmonary function and exacerbations, evaluated by the person conducting the interview. With regard to GINA guidelines patients were categorised as having controlled asthma when they had no limitation of daily activities, nocturnal symptoms and exacerbations, had none or twice or less a week of daytime symptoms and need for rescue medications as well as normal lung function (FEV1 > 80% predicted). Partly controlled were patients having any of the following – limitation of activities, nocturnal symptoms/awakenings, more than twice a week had symptoms during the day and required reliever medication, had one or more exacerbation per year and FEV1 below 80% predicted. All subjects who reported three or more of the features of partly controlled disease or exacerbation in any week were regarded as uncontrolled asthmatics.

The general characteristics of the participants in the study as well as smoking status and body mass index are presented in Table 1. The studied populations did not differ in terms of smoking status. As for BMI there were significantly more asthmatics in the range of obesity i.e. having BMI above 30 (25.4% vs 12.8%, p < 0.001) than controls. Also, the women tend to be more represented in the asthmatic sample (61.8% vs 53.2% in the RDF controls sample) but this is in accordance with the literature data about sex difference in asthma prevalence [22]. Furthermore, risk factor analysis showed that female gender and BMI > 30 increase the risk of having uncontrolled asthma (Table 2).

The respiratory symptoms reported in the last 12 months were significantly pronounced in the asthmatic group compared to the RDF group (Table 3). The most prevalent symptoms were wheezing (79.2% vs 9.2%), wheezing with shortness of breath (58.7% vs 1.3%) and morning cough (42.5% vs 15.5%), followed by productive cough (36.1% vs 6.8), shortness of breath (36.1% vs 2.5%) and longstanding cough (32.5% vs 11.1%), all significant at p < 0.001. Additionally, when longstanding or morning cough were evaluated in the absence of shortness of breath and wheezing, asthmatic subjects were significantly less than the RDF control group (1.9% vs 7.8% and 3.1% vs 11.2%, respectively) (Figure 2a). This observation accounts for the multilayered nature of the asthmatic condition and poses question on the appraisal of a disease presenting only with cough. When reporting different types of cough, asthmatics have clustered complaints (Figure 2b), and report having productive cough always coupled with longstanding and/or morning cough. We also found that productive, morning and longstanding cough increased the risk of having partly or uncontrolled disease (Table 2). Control subjects, on the other hand, have less frequent complaints and tend to report them as separate symptoms, with very few (0.9%) having morning cough, productive cough and longstanding cough at the same time.

Allergic rhinitis is reported in 73.8% of the asthmatic subjects, compared to 30.7% of the RDF control group, and allergic rhinitis and cough are present in 22.8% of the asthmatics but in only 4% of the controls.

The results from the pulmonary function tests, skin-prick tests and health-care visits are summarised in Table 4. The mean value of pre-bronchodilator FEV1% predicted in the asthmatics is 90.6 ± 17.6 (standard deviation) versus 101 ± 12.9 in the control group (Figure 3). Increase of the FEV1 with ≥ 12% and 200 ml after inhalation of a bronchodilator was noted in 24.8% of the asthmatics and 3.4% in the RDF controls. Low lung function, estimated as having FEV1 below 80% predicted, was present in 23.2% in the asthma group, but only is 5.3% in the respiratory disease-free group. Proportion of asthmatics that react with decrease of the FEV1 more than 20% after inhaling a cumulative dose of 1.96 mg of methacholine is 70.9%, but still 32% of the control group also shows increased reactiveness of their airways (Figure 4).Subjects with asthma that had at least one positive skin-prick test were 71.8% of those who had the test performed (575 subjects) and 33.1% of the controls showed positive results (from 577 subjects tested). Moreover, when sensitisation was present in the asthmatics it was often to four or more allergens highlighting a noticeable polysensitisation in comparison to the respiratory disease-free subjects (Figure 5).

Over a period of one year, 35.3% of the asthmatics reported to have sought medical services for respiratory symptoms, 2.2% were hospitalised and 10.6% reported emergency care visits, while the corresponding percentage in the RDF control group was 9.5%, 0.1% and 1.3% respectively.

The studied asthmatic population also outlined for the presence of respiratory comorbidities, characterised by the use of asthma medications and the level of asthma control that the subjects have maintained for the last 12 months (Table 5). Physician diagnosed chronic bronchitis was present in 11.3% of the asthma group, chronic obstructive pulmonary disease was reported by 5.8% and emphysema by 0.7%.

From the asthmatics, 87.5% reported using some type of asthma medication (Figure 6). Inhaled corticosteroids (ICS) used alone or in combination with SABA and/or LABA, represented 60.2% of the utilised medications. SABAs as a sole treatment modality were used by 27.2% of the asthmatics. In respect to the level of asthma control, subjects were designated as having controlled, partly controlled or uncontrolled disease according to Global Initiative for Asthma (GINA) 2006 criteria. 41.6% of the asthmatics had controlled disease, still 40.6% were partly controlled and 17.8% of an uncontrolled asthma. We also evaluated how frequent different types of cough were present in the asthmatic subjects who were stratified on the level of control (Table 6). Morning cough was present in the 46% of the partly controlled and 68.1% in the uncontrolled subjects, productive cough – in 38.2% and 68.1% in these groups, respectively and longstanding cough in 33.1% of the partly and 55.5% of the uncontrolled asthmatics.