Role of hydrogen sulphide in airways

Table 1 Hydrogen sulfide concentration in healthy subjects and patients with asthma, chronic obstructive pulmonary disease or pneumonia

Subjects	Age(yr)	H2S concentration in serum/plasma (μmol/L)	Ref.
Healthy
	71-80	35.7 ± 1.2	[16]
	61-70	34.0 ± 0.9	[16]
	50-60	36.4 ± 1.1	[16]
	64.1 ± 8.7	35.4 ± 5.3	[43]
	9.22 ± 1.80	52.60 ± 5.56	[17]
Patients with bronchial asthma
Bronchial asthma	6-12	44.17 ± 10.95	[17]
Neutrophilic group	53.0 ± 13.9	8.8 ± 4.7	[46]
Paucigranulocytic group	45.5 ± 15.7	6.9 ± 2.0	[46]
	9.03 ± 1.84	44.17 ± 10.95	[17]
Patients with stable COPD
Patients with acute exacerbations of COPD
	73.9 ± 8.3	33.8 ± 18.6	[43]
Patients in stage I to II	65.6 ± 1.6	40.5 ± 6.3	[16]
Patients in stage III		33.4 ± 2.9	[16]
Patients in stage IV		27.6 ± 1.6	[16]
Patients with pneumonia	57.6 ± 20.4	22.7 ± 14.6	[43]
		H2S concentration in exhaled air (ppb)
Healthy	52.86 ± 19.81	8.0-16.0	[18]
Patients with bronchial asthma
Eosinophilic group	46.0 ± 15.2	7.7 ± 4.2	[46]
Paucigranulocytic group	45.5 ± 15.7	11.1 ± 4.6	[46]
Patients with COPD
Acute exacerbations	67.5 ± 11.47	8.0-13.0	[18]
Stable COPD	64.11 ± 8.79	9.0-12.0	[18]

H₂S: Hydrogen sulfide; COPD: Chronic Obstructive Pulmonary Disease.

Table 2 The effect of hydrogen sulfide on airway smooth muscle function

Tissue	H2S effects	Involved mechanism	Ref.
Porcine peripheral bronchiols	Relaxation	Alteration in K+ channels activity	[20]
Guinea pig main bronchus	Slight relaxation		[21]
Guinea pig airways	Neurogenic inflammatory responses	Stimulation of TRPV1 receptors on sensory nerves endings	[23]
Mouse main bronchus	Relaxation	Independent of NK1/NK2 tachykinin receptors, KATP channels, production of NO, cGMP and prostaglandins	[21]
Mouse lung	Neurogenic inflammation	Stimulation of NK1 and Substance P release	[24]
Mouse small intrapulmonary airways	Relaxation	Inhibition of Ca2+ release from intracellular stores through InsP3 receptors	[27]
Mouse tracheal smooth muscle cells	Relaxation	Activation of BKCa channels	[26]
Rat trachea	Relaxation	Independent of KATP channels, β-adrenoceptors, epithelium and production of NO, cGMP and prostaglandins	[22]
Human ASMCs	Relaxation	Opening of KATP channels	[29]
Isolated human airway smooth muscle cells	Relaxation	Inhibition of ERK-1/2 and p38 MAPK phosphorylation	[30]
	Decrease of cell proliferation and IL-8 release

H₂S: Hydrogen sulfide; TRPV: Transient receptor potential vanilloid channels.

Table 3 Implication of hydrogen sulfide in the pathophysiology in human airway diseases - its use as a biomarker

Disease
COPD	Higher serum H2S level in patients with COPD compared with healthy subjects[16]
	Acute exacerbation of COPD decreases serum H2S level compared to patients with stable COPD[16,42]
	Higher sputum H2S levels in patients with acute exacerbation of COPD compared to those with stable COPD[42]
	Higher sputum-to-serum ratio of H2S in COPD subjects with acute exacerbation comparative with those with stable disease[42]
	Lower serum H2S levels in patients with COPD who required antibiotics treatment[43]
Asthma	In children, serum H2S concentration was significantly decreased compared to healthy subjects and correlated positively with FEV1[17]
	In adults, exhaled H2S was lowest in eosinophilic asthma correlated positively with FEV1[46]
Pulmonary fibrosis	H2S suppress human fibroblast migration, proliferation and phenotype transform stimulated by fetal bovine serum and growth factors and inhibits the TGF-β1-induced differentiation of fibroblasts to myofibroblasts[53]

H₂S: Hydrogen sulfide; COPD: Chronic Obstructive Pulmonary Disease; FEV₁: Forced expiratory volume during first second; TGF-β₁: Transforming growth factor beta 1.