Extending the data collection from a clinical trial: The Extended Salford Lung Study research cohort

The Ext-SLS study population

Overall, 1183/7032 participants (18.9%) from the SLS ITT population consented to the Ext-SLS and 1147 of these (n = 798 asthma, n = 349 COPD) completed questionnaires and had primary care data available for analysis. The SLS ITT populations included 4233 asthma patients and 2799 COPD patients. While the intention was to collect full retrospective EHR data, ultimately, only ~10 years of data (including retrospective and some prospective) data were obtained and are available. Participants consented to the Ext-SLS a mean of 3.2 years post-SLS. In the SLS, patients were randomized 1:1 to FF/VI versus UC. In the Ext-SLS, 46% (368) of participants with asthma and 48% (167) of participants with COPD were originally randomized to FF/VI during the SLS. Most Ext-SLS participants were from Salford (51%; n = 582) or Trafford (30%; n = 341) and provided consent in 2018 (91%; n = 1039).

Descriptive comparison of Ext-SLS and SLS ITT populations

Baseline demographics collected at the beginning of the SLS were broadly similar between the Ext-SLS and SLS cohorts (Table 2), with some exceptions. Among participants with asthma, the proportion aged >50 years at baseline was higher in the Ext-SLS cohort compared with the SLS cohort (p < 0.0001). Conversely, at entry to the SLS, participants in the Ext-SLS cohort with COPD were, on average, slightly younger at baseline than in the SLS COPD ITT population, with a greater proportion of participants aged <50 years (p = 0.0013). Compared with SLS asthma participants, there were more females in the Ext-SLS (p = 0.0035), and a larger proportion reported never smoking at baseline (p = 0.007). For participants with COPD, there was a greater proportion of “ex-smokers” and a smaller proportion of “current smokers” in the Ext-SLS cohort compared with the SLS cohort; however, these differences were not statistically significant.

Table 2 Baseline characteristics of the Ext-SLS cohort and SLS ITT populations, as recorded at the time of entry into the SLS.

Respiratory disease characteristics for asthma (Table 3) and COPD (Table 4) were broadly similar between the SLS and Ext-SLS cohorts, but with some notable differences. Participants with asthma in the Ext-SLS potentially had less severe disease at SLS entry, compared with the SLS asthma cohort, based on self-reported symptoms, control as measured using the ACT and short-acting β2-agonist (SABA) reliever therapy use (Table 3). Participants with COPD in the Ext-SLS had slightly better lung function, lower CAT scores (a greater proportion of participants with scores below 10), and a smaller proportion of the Ext-SLS cohort were GOLD Grade 3 or 4 (Table 4).

Table 3 Asthma disease characteristics in the Ext-SLS cohort and SLS ITT populations, captured at entry to the SLS.Table 4 COPD disease characteristics in the Ext-SLS cohort and SLS ITT populations, captured at the entry to the SLS.Description of select Ext-SLS primary care data

A selection of variables relevant to asthma and COPD are described here, illustrating the breadth of information available.

Table 5 shows BMI measurements recorded in participants’ primary care EHR; most asthma and COPD participants were overweight (BMI ≥25 kg/m2) or obese (BMI ≥30 kg/m2). Average BMI measurements in Ext-SLS (at or just prior to the time of consent) reflected measurements recorded at SLS entry (asthma 29.9 and 29.9; COPD 28.1 and 27.8, respectively; Table 2).

Table 5 Most recent BMI result and self-reported smoking status recorded in primary care EHR in the 24 months prior to Ext-SLS consent.

The smoking status of participants in the Ext-SLS showed that, among participants who had been smokers at SLS baseline, 46% of those with asthma and 31% of those with COPD had stopped smoking (Table 5).

Common conditions (ever recorded in EHR) among Ext-SLS asthma participants included atopy (57.0%), pneumonia (53.8%), and diabetes mellitus (14.9%) (Table 6). Evidence of current asthma (defined based on the presence of an asthma medical code in the 12 months preceding Ext-SLS consent) was observed in 86.2% of the asthma group. Two participants had no medical information available, meaning 99.7% of the asthma group were confirmed as having ever had asthma (i.e., any record of asthma prior to Ext-SLS consent).

Table 6 Select medical conditions ever recorded in Ext-SLS primary care EHR data up to and including the date of Ext-SLS consent.

Among Ext-SLS COPD participants, comorbidities included pneumonia (68.5%), atopy (37.0%) and arrhythmia (26.1%). In the 12 months prior to Ext-SLS consent, 21.5% of COPD participants had evidence of current asthma, while 37.2% had no prior asthma diagnosis (Table 6).

A large proportion of asthma and COPD participants had records for blood eosinophil (66 and 83%, respectively) and neutrophil counts (68 and 86%, respectively); with many having multiple measures (mean 2.2 asthma, 2.6 COPD) in the 24 months prior to Ex-SLS consent. Compared with asthma participants, a slightly higher proportion of COPD participants had blood eosinophil counts ≥150/μl (69 versus 66%). Neutrophil counts <6000/μl were recorded for 88% of asthma participants and 77% with COPD.

Among the 349 Ext-SLS COPD participants, 75% had information on GOLD airflow grade; most participants were GOLD Grade 2 (43%). An average of three (range 1–12) FEV1 measurements were taken in the 24 months prior to consent.

Prescriptions of respiratory medicines in the 12 months prior to Ext-SLS consent are detailed in Table 7. A high proportion of asthma and COPD participants were prescribed SABA (83 and 90%, respectively). This was also the case for inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) fixed-dose combinations (78 and 88%, respectively). Leukotriene receptor antagonists were prescribed to 15% of asthma participants, while 25% of COPD participants were prescribed a single-inhaler triple therapy.

Table 7 Respiratory medicines prescribed in the 12 months prior to Ext-SLS consent, as recorded in primary care HER.Description of participant-completed questionnaires

All participants completed some of the questionnaires, with most participants completing all required questions (asthma: 616 [77%]; COPD: 221 [63%]). The distribution of responses for each question was similar when analyzing the responses from all patients who completed the question compared to the subset of patients who completed all required questions (Tables S1,S2).

Asthma

Among those who answered disease history questions (n = 738–755, variable number of responders), 31% reported the first occurrence of symptoms at age ≥40 years. The first diagnosis was made ≥40 years of age for 35% of patients, with 40% prescribed medication for the first time aged ≥40 years. Among the participants with asthma who responded to smoking questions (n = 784), 12% identified as current smokers (compared with 14% at SLS baseline and 14% as recorded in the primary care EHR data; Table 2).

The Asthma Control Test (ACT) was completed by 787 participants, 61% of whom scored ≥20 suggesting their asthma was well-controlled at the time of consent into the Ext-SLS. Scores suggesting partially controlled (ACT score 16–19) and uncontrolled (ACT score <16) asthma were found in 20 and 19% of participants, respectively. Of the 789 participants who completed the Asthma Control Questionnaire-6 (ACQ-6), 37% scored ≤0.75, indicating controlled asthma, while 31% scored >0.75 and <1.5 suggesting partial control and 32% scored ≥1.5 suggesting uncontrolled asthma. The effect of asthma on sleep, as measured by the COPD and Asthma Sleep Impact Scale (CASIS) total score, was found to be low among the Ext-SLS participants (n = 793), with 87% scoring <60 out of 100, placing them in the first tertile—indicating low impact (Fig. 1).

Fig. 1: Disease impact on sleep among participants with asthma and COPD as reported at the time of Ext-SLS consent.figure 1

CASIS COPD and Asthma Sleep Impact Scale, COPD chronic obstructive pulmonary disease, Ext-SLS extended Salford Lung Study. Note: aOne week look-back period for all seven questions. Asthma responders n = 783–792, COPD responders n = 335–343, variable per question.

Commonly reported triggers for asthma symptoms were airway infections and colds (88%), dust (85%), exercise (77%), and cold air (70%) (Fig. 2). Alterations to maintenance medication dose or frequency were made without GP input by 25% of 783 participants, with 51% doing this ≥3 times in the preceding six months. The majority of responders had never been prescribed an oral corticosteroid rescue pack (82% of 759 participants) nor received a written asthma management plan (67% of 717 participants).

Fig. 2: Common symptom triggers as reported by Ext-SLS participants with asthma at the time of Ext-SLS consent.figure 2

Ext-SLS extended Salford Lung Study. Note: aOf the airway. Responders providing a “Yes” or “No” answer n = 589–760 variable per question.

COPD

A large proportion of responders (87% of 340) reported early exposure to second-hand tobacco smoke. For 66% of 342 participants, their mother was a smoker (Table S2). Among the participants with COPD who responded to smoking questions, 38% were classified as current smokers (compared with 46% at SLS baseline and 38% in the primary care EHR data). Among the participants who had ever smoked, 60% reported beginning smoking on most days between the ages of 15 and 19 years. When asked about environmental exposures, in the 93% of participants who had ever been employed, common exposures in the workplace were dust, cigarette smoke and fumes (including chemical fumes) (Fig. 3).

Fig. 3: Self-reported working environments for participants with COPD in the Ext-SLS who reported working outside the home.figure 3

COPD chronic obstructive pulmonary disease, Ext-SLS Extended Salford Lung Study. Note: Responders n = 337–346 variable per question.

The mean (SD) COPD Assessment Test (CAT) score, among participants with COPD who completed this part of the questionnaire (n = 333), was 22.7 (8.7). Overall, 61% of participants scored >20, denoting a high impact of disease; the largest proportion of participants scored 21–30 (40%)—with lower scores denoting less disease burden. Based on the CASIS, most responders (n = 343) reported the little effect of their disease on sleep, with the majority (67%) scoring <60 out of 100 (first tertile, low impact on sleep) (Fig. 1). Among the other participants, 13% scored 60–70 (second tertile) and 20% scored ≥71 (third tertile). Most responders (37%) scored 1 on the modified Medical Research Council (mMRC) dyspnea scale, followed by 2 (29%).

In response to questions on social and physical functioning (n = 331–346, variable number of responders), 76% of participants reported visiting friends or family at least once per week; while 36 and 37% described being moderately satisfied and not at all satisfied with their health, respectively. Overall, 36% of participants reported feeling tired nearly every day, 16% on more than half of the days and 34% on several days in the two weeks prior to answering the questionnaire. Pub or social club attendance was reported by 29% of participants, 11% attended a sports club, gym, or golf club, 14% attended other group activities at least once per week but 53% reported that they did not attend any of the activities listed in the questionnaire. Being unable to walk unaided was described by 33% of participants, with COPD being a factor in the need for assistance in 88%.

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