A1. Classification and Description of Medications

Supplemental material

Medication Group ATC code ATC class

Antihypertensives C02A Antiadrenergic agents, centrally acting C02C Antiadrenergic agents, peripherally acting C02D Arteriolar smooth muscle, agents acting on C02N Combinations of antihypertensives in ATC-group C02 C03A Low-ceiling diuretics, thiazides C03B Low-ceiling diuretics, excluding thiazides C03C High-ceiling diuretics C03E Diuretics and potassium-sparing agents in combination C07 Beta blocking agents C08 Calcium channel blockers C09A ACE inhibitors, plain C09B ACE inhibitors, combinations C09C Angiotensin II antagonists, plain C09D Angiotensin II antagonists, combinations

Antacids A02A Antacids A02B Drugs for peptic ulcer and gastro-oesophageal reflux disease

Anxiolytics N05B Anxiolytics

Hypnotics N05C Hypnotics and sedatives

Antidepressants N06A Antidepressants

Antasthmatics R03 Drugs for obstructive airway diseases

Description of Medication Types: Antihypertensives are a range of drugs aimed at lowering blood pressure thus decreasing the risk of stroke, coronary events, heart failure and renal failure; antacids are a group of drugs used to relieve symptoms of ulcer dyspepsia and of non-erosive gastro-oesophageal reflux as well as non-ulcer dyspepsia; anxiolytics can be prescribed to alleviate anxiety states through sedation; hypnotics are used to induce sleep; antidepressants are used in the treatment of depression and antasthmatics are used in the management of asthma and chronic obstructive pulmonary disease. A2. HYENA study population characteristics stratified by exposure to night-time aircraft noise (L night). Percentages are calculated within each band of exposure.

Lnight Aircraft (dB)

30-39.9 40-49.9 50-59.9 >=60 Total

Population Characteristics

N 2290 1396 862 93 4641

Females (%) 50.0 50.9 51.6 37.7 50.3

Age (mean ± sd) 57.7 ±7.0 58.0 ±7.3 57.5±7.0 57.9±6.5 57.7 ±7.1

BMI (mean ± sd) 26.9 ±4.6 27.2 ±4.5 27.3 ±4.7 28.4 ±4.9 27.1 ±4.6

Alcohol units/wk (mean ± sd) 6.8±9.5 5.9±8.3 6.2±9.1 5.7±9.7 6.4±9.1

Physical activity

Education highest quartile (%) 28.0 24.3 15.2 12.9 24.2

Non-smokers (%) 39.6 40.8 41.1 57.0 40.6

Highly annoyed by aircraft noise night (%) 9.0 26.8 27.2 44.1 18.4

Country (% within each exposure band)

UK (%) 5.8 9.5 27.3 91.4 12.6

Germany (%) 22.5 14.8 28.4 4.3 20.9

Netherlands (%) 18.0 14.4 29.5 4.3 18.8

Sweden (%) 26.5 19.1 13.5 0 21.3

Greece (%) 8.0 30.3 0.9 0 13.3

Italy (%) 19.3 12.0 0.5 0 13.2

Total (%) 100.1 100.1 100.1 100.0 100.1 sd: standard deviation A3. HYENA study population characteristics stratified by exposure to 24hr road traffic noise (LAeq,24h). Percentages are calculated within each band of exposure.

LAeq,24h Road traffic (dB) 45-54.9 55 – 64.9 >=65 Total

Population Characteristics

N 3060 1176 406 4642

Females (%) 50.2 51.5 47.8 50.3

Age (mean ± sd) 57.7 ±7.1 57.7 ±7.2 57.6±7.0 57.7±7.1

BMI (mean ± sd) 27.2 ±4.5 27.0 ±4.7 27.0 ±4.8 27.1 ±4.6

Alcohol units/wk (mean ± sd) 6.2±8.6 6.9±10.0 6.8±9.7 6.4±9.1

Physical activity

Education highest quartile (%) 25.7 21.0 22.2 24.2

Non-smokers (%) 42.0 38.1 37.2 40.6

Highly annoyed by road traffic noise (%) 5.8 16.9 37.7 11.4

Country (% within each exposure band)

UK (%) 15.4 9.4 0.7 12.6

Germany (%) 13.9 31.6 42.4 20.9

Netherlands (%) 17.0 24.3 16.3 18.8

Sweden (%) 25.8 15.0 6.7 21.4

Greece (%) 18.1 4.2 3.0 13.3

Italy (%) 9.9 15.6 31.0 13.2

Total (%) 100.1 100.1 100.1 100.2

sd: standard deviation A4. Comparison of country-specific ORs (95% CIs) for antihypertensive use in relation to aircraft noise (LAeq,16h and Lnight) between highly annoyed and not highly annoyed groups.

Medication Group Noise Source Country Annoyance OR 95% CI N (with aircraft noise in day) Antihypertensives LAeq,16h Aircraft UK Highly annoyed 1.63 (1.15, 2.33) 215 Not highly annoyed 1.12 (0.93, 1.35) 385 Germany Highly annoyed 1.16 (0.81, 1.67) 217 Not highly annoyed 1.02 (0.89, 1.18) 755 Netherlands Highly annoyed 1.67 (0.97, 2.87) 164 Not highly annoyed 0.96 (0.77, 1.18) 736 Sweden Highly annoyed 0.69 (0.34, 1.39) 246 Not highly annoyed 0.85 (0.73, 1.00) 757 Greece Highly annoyed 1.01 (0.66, 1.54) 337 Not highly annoyed 1.00 (0.80, 1.26) 301 Italy Highly annoyed 0.79 (0.51, 1.22) 209 Not highly annoyed 0.76 (0.64, 0.91) 544

(with aircraft noise at night) Antihypertensives Lnight Aircraft UK Highly annoyed 1.49 (1.14, 1.94) 190 Not highly annoyed 1.14 (1.00, 1.31) 410 Germany Highly annoyed 1.04 (0.76, 1.41) 142 Not highly annoyed 1.01 (0.91, 1.11) 830 Netherlands Highly annoyed 1.29 (0.95, 1.75) 102 Not highly annoyed 1.13 (1.01, 1.26) 798 Sweden Highly annoyed 1.25 (0.88, 1.79) 89 Not highly annoyed 1.05 (0.95, 1.17) 914 Greece Highly annoyed 1.13 (0.85, 1.52) 242 Not highly annoyed 1.02 (0.89, 1.16) 398 Italy Highly annoyed 0.99 (0.75, 1.31) 136 Not highly annoyed 0.91 (0.82, 1.01) 618

OR: odds ratio 95% CI: 95% confidence interval The hierarchical structure of each logistic regression model assumed a random intercept that accounts for differences in the use of medication between countries and a random slope to account for differences between countries in the effect of aircraft noise on medication use, and adjustment was made for age, sex, BMI, alcohol intake, education, exercise and smoking status. The odds ratios were calculated for two groups (highly annoyed and not highly annoyed by aircraft noise) by running each hierarchical model for each group.

For each of the aircraft noise models (LAeq,16h and Lnight), adjustment was made for exposure to road traffic noise (LAeq,24h). A5. Comparison of ORs (95% CIs) for medication use (except antihypertensives) in relation to aircraft noise (LAeq,16h and Lnight) between highly annoyed and not highly annoyed groups.

Medication Group Noise Source Annoyance OR 95% CI N (with aircraft noise in day) Antacids LAeq,16h Aircraft Highly annoyed 1.26 (0.84, 1.90) 1331 Not highly annoyed 0.99 (0.85, 1.15) 3311 Anxiolytics or

Hypnotics LAeq,16h Aircraft Highly annoyed 1.25 (0.83, 1.90) 1331 Not highly annoyed 0.95 (0.78, 1.17) 3311

Anxiolytics LAeq,16h Aircraft Highly annoyed 1.17 (0.71, 1.94) 1331 Not highly annoyed 1.11 (0.85, 1.46) 3311

Hypnotics LAeq,16h Aircraft Highly annoyed 1.64 (0.80, 3.36) 1331 Not highly annoyed 0.80 (0.60, 1.06) 3311

Antidepressants LAeq,16h Aircraft Highly annoyed 1.04 (0.64, 1.71) 1331 Not highly annoyed 0.97 (0.79, 1.19) 3311

Antasthmatics LAeq,16h Aircraft Highly annoyed 1.13 (0.69, 1.87) 1331 Not highly annoyed 1.05 (0.87, 1.26) 3311

(with aircraft noise at night)

Antacids Lnight Aircraft Highly annoyed 1.60 (1.16, 2.22) 855 Not highly annoyed 1.04 (0.90, 1.21) 3784 Anxiolytics or Hypnotics LAeq,16h Aircraft Highly annoyed 1.16 (0.79, 1.71) 855 Not highly annoyed 0.99 (0.81, 1.21) 3784 Anxiolytics Lnight Aircraft Highly annoyed 1.15 (0.69, 1.91) 855 Not highly annoyed 1.14 (0.88, 1.49) 3784 Hypnotics Lnight Aircraft Highly annoyed 1.29 (0.68, 2.44) 855 Not highly annoyed 0.78 (0.59, 1.04) 3784 Antidepressants Lnight Aircraft Highly annoyed 0.95 (0.60, 1.50) 855 Not highly annoyed 0.98 (0.81, 1.18) 3784 Antasthmatics Lnight Aircraft Highly annoyed 1.10 (0.75, 1.62) 855 Not highly annoyed 1.01 (0.85, 1.21) 3784

OR: odds ratio 95% CI: 95% confidence interval The hierarchical structure of each logistic regression model assumed a random intercept that accounts for differences in the use of medication between countries and adjustment was made for age, sex, BMI, alcohol intake, education, exercise and smoking status. The odds ratios were calculated for two groups (highly annoyed and not highly annoyed by aircraft noise) by running each hierarchical model for each group.

For each of the aircraft noise models (LAeq,16h and Lnight), adjustment was made for exposure to road traffic noise (LAeq,24h).