TABLE 2.

Reported cough cases after administration of some antibiotic inhalation products in clinical studies

Drug	Formulation	Dose	Regimen	Delivery platform	Subjects	Reported coughs	Reference
Tobramycin	Powder	112 mg (4 capsules)	Twice daily	T‐326 dry powder inhaler	Cystic fibrosis	• 48% (powder) • 31% (solution) • Higher cough incidents in all age groups receiving powder	(Geller et al., 2014; Konstan et al., 2011)
	Solution	300 mg in 5‐ml saline	Twice daily	PARI LC PLUS® air jet nebuliser
Tobramycin	Powder	112 mg (4 capsules)	Twice daily	T‐326 dry powder inhaler	Cystic fibrosis	• 20% (powder) • 0% (solution) • Increased cough incident with increased powder dose	(Geller, Konstan, Smith, Noonberg, & Conrad, 2007)
	Solution	300 mg in 5‐ml saline	Twice daily	PARI LC PLUS air jet nebuliser
Tobramycin	Solution	300 mg in 5‐ml saline	Twice daily for 28 days	PARI LC PLUS air jet nebuliser	Bronchiectasis	• 41% (tobramycin solution) • 24% (placebo)	(Barker et al., 2000)
		Placebo (1.25 mg of quinine sulfate in saline)
Tobramycin (radiolabelled)	Solution	300 mg in 5‐ml saline	Single dose	eFlow rapid or PARI LC PLUS air jet nebuliser	Cystic fibrosis	• 50% (eFlow rapid) • 17% (PARI LC PLUS)	(Lenney, Edenborough, Kho, & Kovarik, 2011)
Tobramycin	Solution	300 mg in 5‐ml saline	Twice daily, 14‐day on/off cycle; 3 cycles	PARI LC PLUS air jet nebuliser	Severe bronchiectasis	• 44% (27%: thought to be treatment related)	(Scheinberg & Shore, 2005)
Tobramycin	Solution	300 mg in 5‐ml saline	Twice daily, 28‐day on/off cycle; 1 + 6 cycles	PARI LC PLUS air jet nebuliser	Cystic fibrosis	• 6.4% (300 mg per 4 ml) • 6.0% (300 mg per 5 ml)	(Mazurek et al., 2014)
		300 mg in 4‐ml saline
Tobramycin	Solution	300 mg in 5‐ml saline	Phase 1: twice daily for 14 days + once a day on Day 15 using one type of nebuliser	eFlow rapid or PARI LC PLUS air jet nebuliser	Cystic fibrosis	• 12% (eFlow) • 0% (PARI LC PLUS)	(Hubert et al., 2009)
			Phase 2: twice daily for 14 days + once a day on Day 15 using other type of nebuliser
Tobramycin	Powder	112 mg (4 × 28‐mg capsules)	Group A Phase 1: tobramycin solution, twice daily for 28‐day on/off Phase 2: tobramycin powder, twice daily for 28‐day on/off	T‐326 dry powder inhaler or patients' personal nebuliser	Cystic fibrosis	• Group A: not reported • Group B: comparable • Group C: post‐inhalation rates reduced from 55% during Phase 1 down to 37% in Phase 2	(Greenwood et al., 2017)
	Solution	300 mg in 3‐ml saline	Group B Phase 1: colistin solution, twice daily for 56 days Phase 2: tobramycin powder, twice daily for 28‐day on/off
Colistimethate sodium	Solution	1 or 2 million units	Group C Phases 1 and 2: tobramycin powder, twice daily for 28‐day on/off
Tobramycin	Powder	112 mg (4 × 28‐mg capsules)	Twice daily, 28‐day on/off cycle; 3 cycles	T‐326 dry powder inhaler	Cystic fibrosis	Cycle 1 • 13% (tobramycin powder) • 27% (placebo) Cycles 2 and 3 • 26% (tobramycin powder) • 24% (placebo)	(Konstan, Geller, et al., 2011)
		Placebo: 112 mg of excipients	Cycle 1: tobramycin powder or placebo
			Cycles 2 and 3: open‐label tobramycin powder
Colistin	Powder	25 mg	A single dose at each visit	In‐house built dry powder inhaler or Ventstream® jet nebuliser	Cystic fibrosis	• Moderate to severe (powder) • No coughs reported (solution)	(Le Brun et al., 2002)
	Solution	160 mg in 6‐ml saline
Colistin sulfometate	Solution	160 mg in 6‐ml saline	A single dose	Ventstream® jet nebuliser	Cystic fibrosis	• Severe cough (solistin sulfate) • No coughs reported (colistin sulfometate)	(Westerman, Le Brun, Touw, Frijlink, & Heijerman, 2004)
Colistin sulfate		100 mg in 6‐ml saline
		Both contained an equivalent amount of colistin (67 mg in 6 ml)
Colistimethate sodium	Powder	125 mg	Twice daily, 24 weeks	Turbospin dry powder inhaler or PARI LC PLUS air jet nebuliser	Cystic fibrosis	• 75% (colistimethate sodium powder) • 43% (tobramycin solution)	(Schuster, Haliburn, Doring, & Goldman, 2013)
Tobramycin	Solution	300 mg in 5‐ml saline	Twice daily, three 28‐day courses