TABLE 2.

Summary of current treatments recommended by the European Respiratory Society [2]

Treatment	Evidence of efficacy/treatment recommendations	Side-effects
Non-pharmacological cough control therapy, such as physiotherapy and speech therapy	Few studies of non-pharmacological therapies. Physiotherapy/speech and language (2 months) [101]: reduced subjective cough score compared with placebo treatment (MD 2.8 points; 95% CI 1.3–4.0). Physiotherapy/speech and language (weekly for 4 weeks) [102]: improved LCQ (+1.53 points; 95% CI 0.21–2.85); reduced cough frequency per hour (fold change, 0.59; 95% CI 0.36–0.95); no significant effect on VAS severity or QoL outcomes.	None.
Non-opioid and non-anaesthetic antitussives	Evidence is limited and of variable quality [2, 3, 25].	Vary depending on the treatment used: see literature for details.
ICS and antileukotrienes	Evidence supporting the use of ICS or antileukotrienes is weak [2]. Available trial data are affected by incomplete assessments of asthma, allergy and non-asthmatic eosinophilic bronchitis [3]. ERS recommends a short trial (2–4 weeks).	Sore and dry throats (ICS) [103]. Headache, gastrointestinal disturbances, increased mucus production [104]; neuropsychiatric events (antileukotrienes) [105].
ICS and an LABA	Moderate evidence supporting use in patients with fixed airway obstruction. Salmeterol+fluticasone twice daily [106]: improved cough severity score compared with placebo (scale: 0–4) (MD −0.09; 95% CI −0.17, −0.01). Short-term trials of 2–4 weeks are recommended.	Sore and dry throat (ICS) [103], muscle cramps and muscle twisting (LABA) [103], potential risk of pneumonia with fluticasone in patients comorbid with COPD [107].
Macrolides, e.g. azithromycin	Limited evidence for routine use. Can be considered if chronic bronchitis refractory to other therapy for a 4-week trial [2]. COPD GOLD stage ≥2 and chronic productive cough [108]: improved cough-specific QoL (LCQ; MD 1.3; 95% CI 0.3–2.3; p=0.01).	Nausea, diarrhoea, headaches or changes to sense of taste [109].
Opioids	In a double-blind, placebo-controlled study, slow-release morphine sulphate, 5 mg twice daily, improved the LCQ score by 3.2 points (p<0.01 versus baseline; p<0.02 versus placebo) and reduced cough severity recorded in a daily cough diary (p<0.01 versus baseline) [78].	Constipation, drowsiness, risk of dependency [2, 3, 110].
Tricyclic antidepressants	In a small case series, 72% of patients responded to treatment, as determined by subjective physician assessment of percentage improvement in cough symptoms [111].	Sedation, dry mouth, anxiety [111].
Gabapentin	Significant improvement in LCQ versus placebo in a randomized, double-blind, placebo-controlled trial. Mean between-group difference: 1.80 (95% CI 0.56–3.04; p=0.004) [80]. Reduction in cough frequency versus placebo (1 h of observation). Mean between-group difference: −27.3% (95% CI −51.8 to −2.9; p=0.028) [80]. Reduction in cough severity versus placebo. Mean difference on VAS: −12.23 points (95% CI −23.2 to −1.3; p=0.029) [80].	Confusion, dizziness, dry mouth, fatigue, nausea, blurred vision, cognitive changes [2, 3].
Pregabalin	Improvement in LCQ versus placebo in a randomized, controlled trial (both arms received speech pathology therapy). Mean difference: 3.5 points (95% CI 1.1–5.8; p=0.024) [81]. Improvement in cough severity. Mean difference on VAS: 25.1 (95% CI 10.6–39.6; p=0.002) [81].	Dizziness, fatigue, cognitive changes, nausea, blurred vision [2].

CI: confidence interval; COPD: chronic obstructive pulmonary disease; ERS: European Respiratory Society; GOLD: Global Initiative for Chronic Obstructive Lung Disease; ICS: inhaled corticosteroids; LABA: long-acting bronchodilator; LCQ: Leicester Cough Questionnaire; MD: mean difference; QoL: quality of life; VAS: visual analogue scale.