Study participants

Participants were recruited (February 15–December 12, 2013) from the Kaiser Permanente medical centres in San Francisco and Hayward. Inclusion criteria included age 18–70 years, body mass index (BMI) 18.5–39.9 kg·m⁻², consuming a low-quality diet (defined as score <6 out of 9 total on the DASH concordance index summing nine nutrient targets, including total fat, saturated fat, protein, cholesterol, fibre, magnesium, calcium, sodium and potassium [12]) and confirmation of uncontrolled persistent asthma through a multistage screening process (i.e. electronic asthma registry queries, completion of the Asthma Control Test [13], pre- and post-bronchodilator spirometry, and if necessary, medical chart review by an asthma specialist) (online supplementary table E1). Exclusion criteria included serious medical or psychiatric conditions (e.g. chronic obstructive pulmonary disease, stroke, psychosis) or special life circumstances (e.g. pregnancy, planned relocation). Of the 2241 patients mailed recruitment letters after their primary care provider approved study contact, 805 patients declined participation, 757 were ineligible and 589 were not contactable or nonresponsive. This process yielded the target enrolment of 90 eligible and consenting participants (figure 1).

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FIGURE 1

CONSORT chart. ACQ: Asthma Control Questionnaire. ^#: ACQ score was computed as the mean of the complete seven-item scores (ACQ7) or the six-item scores (ACQ6) if forced expiratory volume in 1 s was missing because spirometry was not performed or not usable per American Thoracic Society standards.

Randomisation and blinding

Participants were randomly assigned in a 1:1 ratio to receive the DASH intervention (n=46) or no intervention (n=44) while all participants continued usual care. Using a Web-based random allocation system [14], we applied Pocock’s minimisation, a covariate-adaptive randomisation method [15], to achieve better-than-chance between-treatment balance across six prognostic factors (age, sex, race/ethnicity, smoking status, DASH concordance index and the seven-item ACQ score). Efron’s biased-coin method [16] was employed to protect allocation concealment with use of non-extreme randomisation probabilities (i.e. 2/3 to 1/3). A designated study staff person who did not have the ability to influence the allocation system’s execution performed randomisation. The trial design precluded blinding participants or interventionists to treatment assignment; however, the investigators, DSMB members, outcome assessors and data analyst were masked throughout the trial.

Treatment arms

Outcome measures

Of the 90 randomised participants, 83 (92%) were assessed at 3 and 6 months (figure 1). All outcome assessors were trained to perform the measurements and interviews per standardised protocols and procedures.

The ACQ [10] integrates seven components of asthma control, including five patient-reported asthma symptoms, reported need for bronchodilators and measured FEV₁; all are scored on a seven-point scale (0–6), with a higher score indicating worse asthma control. The ACQ score was computed as the mean of the seven-item scores (ACQ7) or the six-item scores (ACQ6) if FEV₁ was missing because spirometry was not performed or the test was invalid. Both measures have been validated [10, 19] and we used the same approach in another published asthma trial [20]. There were 90 participants with ACQ scores (88 ACQ7 and two ACQ6) at baseline, 79 (77 and two) at 3 months, and 82 (75 and seven) at 6 months.

Participants also completed the 15-item Mini Asthma-specific Quality of Life Questionnaire (MiniAQLQ) [21]. A change of at least 0.5 points is regarded as clinically significant for both the ACQ and MiniAQLQ [19]. Outcome assessors performed spirometry according to the American Thoracic Society (ATS) standards [22], with ongoing quality monitoring. Two independent respiratory therapists rated all spirograms. A valid test required a minimum of two manoeuvres meeting the ATS acceptability and reproducibility criteria, from among which the best parameter values were chosen for FEV₁ and forced vital capacity (FVC) separately and used in data analyses. Outcome assessors also followed published protocols to obtain weight and blood pressure measurements [23, 24].

For dietary intake, outcome assessors conducted multiple-pass 24-h diet recalls [25], which is the current gold standard for diet assessment, with participants over the phone using the Windows-based Nutrition Data System for Research (Nutrition Coordinating Centre, University of Minnesota, Minneapolis, MN, USA). These data were used to compute participants’ DASH concordance index as a measure of overall diet quality [12]. Participants also completed fasting blood draws at the onsite clinical laboratory for assays of plasma glucose and lipid profile. Atopic status was determined by testing specific IgE antibodies to dust mite (Dermatophagoides pteronyssinus), animal dander (cat and dog), grasses (ragweed and timothy grass) and tree (juniper cedar) using ImmunoCAP Specific IgE (Phadia, Uppsala, Sweden).

Data abstracted from Kaiser Permanente of Northern California electronic health records included encounters with the healthcare system, diagnoses and pharmacy dispensing events during the 6 months before and after randomisation. Participants were interviewed at each follow-up visit about possible adverse events during the past 3 months and the study physician adjudicated the events per study safety protocol.

Overall diet quality and daily goal attainment

Mixed-model-based estimates showed that intervention participants had a significant net-of-control increase of 0.8 (95% CI 0.2, 1.5) in DASH score and 1.9 (0.8, 3.0) daily servings of fruit and vegetables at 6 months (table 2), which were also observed at 3 months (online supplementary table E2). Figure 2 shows the complete fitted distributions and sorted individual values of change in DASH scores. The Cohen’s d estimate based on unadjusted mean±SD changes in DASH scores over 6 months of the two groups was 0.5, suggesting medium intervention effect (figure 3a). In addition, at 6 months intervention participants showed a net mean increase in low-fat/fat-free dairy servings, and net mean decreases in fat and sodium intake, although the 95% confidence intervals included the null. The percentage of intervention participants meeting the minimum daily DASH goals was 33% versus 8% of controls for seven servings of fruit and vegetables, 49% versus 53% for total fat grams at 27% of individualised caloric needs, 23% versus 15% for two servings of low-fat/fat-free dairy products, and 58% versus 40% for ≤2300 mg of sodium. Compared with the control group, the intervention group’s log-transformed odds ratios of reaching the minimum goal were greater for fruit and vegetable servings and sodium intake, although only the latter reached statistically significance (figure 4).

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FIGURE 2

Fitted distributions and sorted values of changes in a, b) Dietary Approaches to Stop Hypertension (DASH) and c, d) Asthma Control Questionnaire (ACQ) scores at 6 months. ^#: DASH scores were calculated based on combining nine nutrient targets (i.e. total fat, saturated fat, protein, cholesterol, fibre, magnesium, calcium, sodium and potassium). The intermediate target of each nutrient was half-way between the DASH target and population mean (based on the National Health and Nutrition Examination Surveys 2007–2008, latest data available at the inception of this study). For a nutrient, participants reaching the DASH target were assigned 1 point, those reaching the intermediate target were assigned 0.5 points and those not meeting the intermediate target were given 0 points. The DASH score was the sum of points for all nine nutrients [12].

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FIGURE 3

a) Baseline DASH, ACQ and MiniAQLQ scores, and their net-of-control improvements at 6 months. b) Percentage of participants meeting minimal clinically significant improvement (0.5) in ACQ and MiniAQLQ at 6 months. DASH: Dietary Approaches to Stop Hypertension; ACQ: Asthma Control Questionnaire; MiniAQLQ: Mini Asthma-specific Quality of Life Questionnaire. ^#: mean±SD; ^¶: covariate-adjusted, mixed-model-based mean (95% CI); ⁺: calculated as unadjusted between-group mean difference in change from baseline to 6 months divided by pooled standard deviation.

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FIGURE 4

Log-transformed odds ratios of intervention participants relative to controls meeting minimum Dietary Approaches to Stop Hypertension intervention goals at 6 months. Bars indicate 95% confidence interval.

TABLE 2

Estimated mean changes from baseline to 6 months in DASH score, asthma outcomes, weight and blood pressure in the intention-to-treat population

	Change from baseline to 6 months
	Baseline	Intervention	Control	Difference
Intervention goal measure
DASH score	2.3±1.3	0.6±0.3	−0.3±0.3	0.8 (0.2, 1.5)
Fruits and vegetables servings per day#	4.4±2.4	1.6±0.5	−0.3±0.5	1.9 (0.8, 3.0)
Fat g·day−1	66.3±40.7	−5.3±4.8	−4.7±4.7	−0.5 (−11.6, 10.5)
Low fat/fat-free dairy servings per day#	1.0±0.9	0.2±0.2	−0.1±0.2	0.3 (−0.1, 0.7)
Sodium mg·day−1	2718±1278	−117±197	−58±192	−58 (−529, 413)
Asthma control
ACQ	1.3±0.8	−0.2±0.1	−0.0±0.1	−0.2 (−0.5, 0.1)
Asthma-specific functional status
MiniAQLQ, overall	5.2±1.1	0.7±0.2	0.2±0.2	0.4 (0.0, 0.8)
MiniAQLQ, symptoms	5.2±1.3	0.6±0.2	0.1±0.2	0.5 (0.0, 0.9)
MiniAQLQ, environment	4.6±1.6	0.7 ±0.2	0.3±0.2	0.4 (−0.1, 1.0)
MiniAQLQ, emotions	4.9±1.5	0.7±0.2	0.3±0.2	0.4 (−0.2, 0.9)
MiniAQLQ, activities	6.0±1.0	0.6±0.2	0.2±0.2	0.3 (−0.0, 0.7)
Spirometry lung function test
FEV1 L	2.6±0.8	−0.0±0.0	−0.0±0.0	0.0 (−0.1, 0.1)
FVC L	3.8±1.0	0.0±0.1	0.1±0.1	−0.0 (−0.2, 0.1)
FEV1/FVC %	68.5±11.3	−0.4±1.1	−1.6±1.0	1.2 (−1.3, 3.7)
Weight and blood pressure
Weight kg	76.5±15.9	−1.2±0.7	−1.1±0.7	−0.1 (−1.8, 1.5)
Body mass index kg·m−2	27.9±4.8	−0.5±0.2	−0.4±0.2	−0.1 (−0.7, 0.4)
Systolic blood pressure mmHg	117.4±14.4	−5.5±1.7	−3.6±1.6	−2.0 (−5.9, 2.0)
Diastolic blood pressure mmHg	74.9±8.9	−1.5±1.1	0.7±1.1	−2.2 (−4.7, 0.4)

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Data are presented as mean±SD (Baseline), covariate-adjusted, mixed-model-based mean±SE (Intervention and Control) or covariate-adjusted, mixed-model-based mean (95% CI) (Difference). DASH: Dietary Approaches to Stop Hypertension (range 0–9 with higher scores indicating better DASH concordance); ACQ: Asthma Control Questionnaire (range 0–6 with higher scores indicating worse asthma control); MiniAQLQ: Mini Asthma Quality of Life Questionnaire; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity.

^#servings were calculated using the Nutrition Data System for Research per the 2000 Dietary Guidelines for Americans (fruit: one serving=1 medium apple, banana, orange or pear, 0.5 cups of chopped, cooked or canned fruit, 0.25 cups dried fruit or 4 fl. oz of fruit juice; vegetables: one serving=1 cup of raw leafy vegetables, 0.5 cups of other cooked or raw vegetables or 4 fl. oz of vegetable juice; dairy: one serving=1 cup of milk or yogurt, 1.5 oz of natural cheese or 2 oz of processed cheese).

Asthma control, asthma-specific functional status and lung function

At 6 months, intervention participants had a net improvement of −0.2 (95% CI −0.5, 0.1) in ACQ score, and consistently favourable changes in MiniAQLQ overall and subdomain scores (figure 3a). The unadjusted Cohen’s d estimates ranged from 0.28 to 0.48 for these asthma outcomes, indicating small-to-medium intervention effects. Significantly higher percentages of intervention participants than controls achieved clinically important improvements of at least 0.5 in ACQ scores (28% versus 9%, p=0.04) and overall MiniAQLQ scores (55% versus 16%, p=0.004) (figure 3b). ACQ and MiniAQLQ results were unaffected by further adjustment for asthma long-term controller (i.e. beclomethasone canister equivalents, a measure of the anti-inflammatory equipotency [27]) or/and short-acting β-agonist (SABA) medication use (i.e. albuterol canister equivalents, a measure of the bronchodilator equipotency) (data not shown).

Spirometric parameters (FEV₁, FVC and FEV₁/FVC), weight and BMI were stable in both groups (table 2). Participants had normal mean blood pressure, fasting plasma glucose and fasting plasma lipids at baseline, with nonsignificant improvements in the intervention relative to the control group (table 2 and online supplementary table E3).

Asthma-related medications and healthcare encounters

Based on pharmacy dispensing records during the 6 months before randomisation, 21% of the 90 participants did not acquire any asthma controller medications, 72% acquired SABAs, 20% had asthma exacerbations requiring systemic corticosteroids, 1% had asthma-related hospitalisations and 11% had asthma-related emergency department visits. The corresponding numbers were 23%, 62%, 13%, 2% and 9%, respectively, during the 6 months after randomisation. The mean±SD beclomethasone canister equivalents of the total acquired long-term controller medications (excluding theophylline and maintenance systemic corticosteroids used for >15 days) were 8.3±8.9 and 7.9±9.0 in 6 months pre- and post-randomisation, respectively. The mean±SD albuterol canister equivalents of the total acquired SABAs were 1.9±2.2 and 1.7±1.9 over the same time periods. Intervention participants showed greater mean increases in long-term controller use and in outpatient visits, whereas they had greater mean decreases in SABA use and in asthma exacerbations requiring systemic corticosteroids; however, the confidence intervals were wide and all included the null (table 3).

TABLE 3

Changes in asthma-related medication use and healthcare encounters^#

	6 months before randomisation			6 months after randomisation			Difference¶
	All participants	Intervention	Control	All participants	Intervention	Control
Subjects n	90	46	44	90	46	44	18 (−5, 40)
Use of long-term controllers	79	74	84	77	80	73	18 (−5, 40)
Type of long-term controllers
ICS alone	27	24	29	25	22	27	0 (−17, 17)
ICS+LABA only	31	33	29	30	35	25	7 (−12, 25)
LTRA alone	7	6	7	9	8	9	0 (−9, 9)
ICS+LTRA	2	0	5	3	2	5	2 (−6, 10)
ICS+LABA+LTRA	12	11	14	10	13	7	9 (−5, 23)
Beclomethasone canister equivalents+	8.3±8.9	7.7±8.9	9.0±9.1	7.9±9.0	8.8±9.9	7.1±8.1	3.0 (−0.4, 6.3)
SABA user	72	76	68	62	59	66	−15 (−36, 6)
Albuterol canister equivalents§	1.9±2.2	1.7±2.1	2.1±2.3	1.7±1.9	1.4±1.7	1.9±2.1	−0.1 (−0.8, 0.5)
Participants with asthma exacerbations requiring systemic corticosteroidsf	20	22	18	13	11	16	−9 (−28, 11)
Total days of systemic corticosteroid supply for asthma exacerbationsf	9.4±6.1	8.6±3.7	10.5±8.5	11.3±5.6	11.4±5.2	11.1±6.3	−1.6 (−16.2, 13.0)
Asthma-related healthcare encounters##
Hospitalisation	1	2	0	2	2	2	−2 (−10, 5)
Emergency department visit	11	9	14	9	7	11	0 (−18, 18)
Outpatient visit	49	46	52	38	43	32	18 (−9, 46)

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Data are presented as mean±SD or %, unless otherwise stated. ICS: inhaled corticosteroid; LABA: long-acting, inhaled β₂-agonist; LTRA: leukotriene modifier; SABA: short-acting β-agonist.

^#extracted healthcare utilisation data from electronic health records included all visits by service type (emergency department, hospital inpatient or outpatient department) to Kaiser Permanente in Northern California and its contracted facilities, and pharmacy dispensing records;

^¶covariate-adjusted, mixed-model-based mean (95% CI) for between-treatment differences in change from 6 months before to 6 months after randomisation;

⁺estimated total number of canisters of beclomethasone to which an asthma controller medication dispensed for a patient in each 6-month period was equivalent in terms of its anti-inflammatory effectiveness (each dispensing of a controller medication (excluding theophylline and systemic corticosteroids used for >15 days), in any form or quantity, was assigned a weight representing its equivalent in fractional or multiple canisters of beclomethasone 80 mg [27]; weighted values were summed for each patient to obtain a cumulative measure of controller medication dose dispensed during the 6 months before and after randomisation separately);

^§estimated total number of canisters of albuterol to which the amount of SABA dispensed in each 6-month period was equivalent in terms of its bronchodilator effectiveness (each SABA medication, in any type or delivery mode, was assigned a weight representing its equivalent in canister of albuterol [27]; weighted values were summed for each patient to obtain a cumulative measure of dose dispensed during the 6 months before and after randomisation separately);

^fdefined as systemic corticosteroids (by tablet, suspension or injection) dispensed for 3–15 days of use;

^##asthma-related healthcare encounters were visits with International Classification of Diseases, ninth revision (Clinical Modification) code 493 as a primary or secondary diagnosis.

We are indebted to the following individuals for their instrumental contributions to the conduct of the study: Veronica Luna, Andrea Blonstein, Elizabeth Jameiro and Nancy Wittels (Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA); Ranna Modir, Jennifer Waldrop and Jodi Thirtyacre (Kaiser Permanente of Northern California, San Francisco, CA, USA). We wish to thank the DASH Data and Safety Monitoring Board members, William Haskell, Ware G. Kuschner and Manisha Desai (Stanford University, Stanford, CA, USA), and extend special thanks to the DASH participants and their families who made this study possible. We also would like to acknowledge Unni C. Nygaard (Stanford University, Stanford, CA, USA) for her comments on the manuscript. The study was conducted while J. Ma was a faculty member at the Palo Alto Medical Foundation Research Institute.

Support statement: This research was supported by grant R34 HL108753 from the National Heart, Lung and Blood Institute, and internal funding from the Palo Alto Medical Foundation Research Institute. P.W. Lavori acknowledges support by the Clinical and Translational Science Award 1UL1 RR025744 for the Stanford Centre for Clinical and Translational Education and Research (Spectrum) from the National Centre for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute. No sponsor or funding source had a role in the design or conduct of the study; collection, management, analysis or interpretation of the data, or preparation, review or approval of the manuscript. Funding information for this article has been deposited with FundRef.