TABLE 2

Murine models involving a combination of exposures to allergens and cigarette smoke (CS)

Strain	Experimental method	Key features of model	First author [ref.]
BALB/c WT	3 weeks of CS (5 days·week⁻¹, 5 cigarettes for 7 min, 4 times·day⁻¹) concurrent with OVA challenge via aerosol for 7 min, 4 times·day⁻¹	↑ serum IgE and IgG1 ↑ eosinophils, lymphocytes and dendritic cells in BALF ↑ dendritic cells, goblet cell hyperplasia, CD4+ and CD8+ T-cells in lung tissue ↑ CCL17 and IFN-γ in BALF ↑ IL-5 in lymph node cell cultures	Moerloose [167]
BALB/c WT	3 weeks of HDM intranasally (5 days·week⁻¹) followed by 2 weeks of concurrent HDM+CS (5 days·week⁻¹, 12 cigarettes for 50 min, 1 or 2 times·day⁻¹)	↓ total cell count, mononuclear cells, neutrophils in BALF ↓ eosinophils in BALF and lung tissue ↓ B-cells and serum IgE ↓ VCAM-1 and eotaxin-1 No significant differences in airway resistance	Botelho [168]
C57BL/6 WT and CD44 deficient	3 weeks of CS (5 days·week⁻¹, 5 cigarettes 3 times·day⁻¹) with HDM intranasally once per week at the end of CS exposure	No significant differences in AHR ↑ CD4+ and CD8+ T-cells, and hyaluronic acid in BALF ↑ goblet cell metaplasia ↑ IL-4, IL-5, IL-13 in lymph node cell culture CD44 deletion resulted in: `o` ↓ number of eosinophils, dendritic cells, neutrophils, CD4+ and CD8+ T-cells in BALF `o` ↓ IL-4, IL-5 and IL-13 in lymph node cell culture `o` ↓ goblet cell metaplasia	Kumar [169]
BALB/c WT	Triple OVA, cockroach antigen, and HDM intraperitoneally on days 0, 14, and 21 followed by 6 weeks of allergen challenge concurrent with CS (5 days·week⁻¹, 4 cigarettes·day⁻¹)	↑ total cell count, eosinophils, macrophages, neutrophils, lymphocytes, IL-4 and IL-5; however, all except neutrophils were higher with allergen alone ↑ IL-10, IL-12, IL-1β, and CXCL1 in BALF ↓ compliance versus control following methacholine challenge, no increase in resistance observed	Tilp [170]
C57BL/6J WT	LPS intranasally at days 0 and 14 followed by 10 weeks of CS (6 days·week⁻¹, 9 cigarettes for 2 h, 2 times·day⁻¹)	Impaired lung function ↑ total cells counts in BALF (↑ neutrophils, lymphocytes and macrophages) ↑ IL-6 and CXCL1 in BALF Goblet cell hyperplasia Bronchial wall thickening	Shu [171]
BALB/c WT	OVA intraperitoneally on days 0 and 14. OVA aerosol administered daily from days 24 to 41 in conjunction to CS (15 cigarettes for 40 min, 2 times·day⁻¹)	↑ total cell count and ↑% of neutrophils in BALF ↑ AHR ↑ serum TNF-α and CXCL1 ↓ HDAC2 but ↑ phosphorylated Akt in lung sections measured using integrated optical density	Xia [172]

WT: wild-type; OVA: ovalbumin; Ig: immunoglobulin; BALF: bronchoalveolar lavage fluid; IFN: interferon; IL: interleukin; HDM: house dust mite; VCAM-1: vascular cell adhesion molecule-1; TNF: tumour necrosis factor; CXCL1: C-X-C motif chemokine ligand 1; LPS: lipopolysaccharide; AHR: airway hyperresponsiveness; HDAC2: histone deacetylase 2; Akt: protein-kinase B.