3. Mannitol versus control ‐ subgroup analysis by dornase alfa use (adverse events).

Adverse event	Dornase alfa users (n = 392)		Dornase alfa non users (n = 208)		P value for test of subgroup differences
	RR	99% CI	RR	99% CI
Cough	1.63	0.68 to 3.92	4.82	0.53 to 43.70	0.24
Haemoptysis	3.06	0.68 to 13.67	2.52	0.15 to 43.23	0.88
Pharyngolaryngeal pain	1.66	0.33 to 8.33	2.71	0.27 to 27.12	0.65
Throat irritation	1.14	0.08 to 16.23	3.13	0.06 to 161.52	0.59
Productive cough	1.59	0.13 to 19.36	1.90	0.03 to 124.54	0.93
Wheezing	0.52	0.07 to 3.62	0.63	0.05 to 8.13	0.88
Asthma	1.40	0.06 to 31.86	0.21	0.00 to 13.84	0.35
Bronchospasm	2.10	0.03 to 138.37	1.90	0.03 to 124.54	0.97
Condition aggravated	1.63	0.43 to 6.28	0.94	0.09 to 9.55	0.59
Chest discomfort	1.38	0.23 to 8.29	0.62	0.02 to 22.39	0.60
Chest pain	0.14	0.00 to 7.43	NA	NA	NA
Vomiting	0.69	0.07 to 6.84	4.44	0.09 to 212.27	0.29
Post‐tussive vomiting	4.72	0.10 to 228.19	2.52	0.15 to 43.83	0.74
Headache	3.87	0.40 to 37.22	1.26	0.06 to 28.54	0.45
Decreased appetite	2.10	0.03 to 138.37	1.90	0.03 to 124.54	0.97
Infections and infestations	0.39	0.10 to 1.51	1.46	0.12 to 17.63	0.23
Musculosketal and connective tissue disorders	2.06	0.18 to 22.87	1.90	0.03 to 124.54	0.97
Skin and subcutaneous disorders	1.61	0.13 to 19.39	3.17	0.06 to 167.04	0.71

CI: confidence interval; NA: not estimable (no events reported in the subgroup); RR: risk ratio.

RR and 99% CI represents the proportion of participants experiencing pulmonary exacerbations pooled across two studies (Aitken 2012; Bilton 2011) (except asthma, bronchospasm, chest pain and decreased appetite reported in Bilton 2011 only).