Table 1.
The Changes of CC16 in pulmonary diseases.
| Disease | Specimen | Change of CC16 | Conclusion | Reference |
|---|---|---|---|---|
| ALI/ARDS | Human; Serum | ↑ | Temporary increased in firefighters after 20 min of smoke inhalation Slightly increased after two hours of riding in cyclists who exposed to photochemical smog No signs of lung impairment were reported |
[20,21,22] |
| ARDS | Human; Serum | ↑ | Higher in non-survivors compared to survivors Positive correlation with severity and mortality |
[23,24] |
| ALI/ARDS | Mice/Rats; Serum | ↑ | A transient elevation of CC16 when animals exposed to O3 or treated with 4-Ipomeanol/alpha-naphtylthiourea | [21,22,29] |
| ARDS | Human; BALF | ↑ | BALF CC16 levels were higher compared to controls | [26] |
| ALI/ARDS | Rats; Airways | ↑ | Lower CC16 concentration after treatment with LPS Lower CC16 messenger RNA expression in an acid aspiration rat model of ALI |
[27,30] |
| BPD | Human; Serum | ↑ | Higher CC16 levels in mechanically ventilated neonates who developed BPD | [34] |
| BPD | Human; Cord blood | ↓ | Lower CC16 concentrations from cord blood predicted the development of BPD in preterm infants | [35] |
| BPD | Human; Airways | ↓ | BALF CC16 level was lower in ventilated neonates who thereafter developed BPD | [36] |
| COPD | Human; Serum | ↓ | Associated with FEV1 decline in most longitudinal studies throughout childhood (BAMSE, MAAS, and CRS birth control studies) or elderly life (LHS, ECLIPSE, TESAOD, ECRHS, and SAPALDIA) Reduced in COPD patients than smoker and non-smoker controls Lower in current than former smoker |
[41,42,43,47] |
| COPD | Human; Airways | ↓ | Airway CC16 expression is inversely correlated with the severity of airflow obstruction in COPD patients | [44,45,46] |
| COPD | Mice; Airways | - | CC16 deficient mice had greater airspace enlargement than WT after CS exposure | [45,46] |
| COPD | Mice; Airways | - | Both WT and CC16 deficient mice developed similar increases in airspace enlargement after CS exposure | [41] |
| COPD | Non-human primates; Airways | ↓ | CC16 expression was downregulated in two different monkey species, Macaca mulatta and Macaca fascicularis, after CS-exposure | [46,48] |
| PF | Human; Serum/Airways | ↑ | BALF and serum levels of CC16 were significantly increased in IPF compared to non-IPF patients and healthy controls | [50,52] |
| PF | Mice | - | CC16 deficient mice developed more severe PF when exposed to Bleomycin | [78] |
| Sarcoidosis | Human; Serum | ↑ | Serum and BALF CC16 increased in individuals with sarcoidosis compared with healthy controls | [57,58,59] |
| Sarcoidosis | Human; BALF | ↑ | BALF CC16 increased in patients with sarcoidosis compared to controls | [58] |
| Sarcoidosis | Human; BALF | No difference | CC16 in BALF was not affected by sarcoidosis | [57,59] |
| Respiratory syncytial virus | Human; Serum | - | Positive association between the serum levels of CC16 and IgG against RSV in atopic athletes compared to non-atopic athletes and healthy controls | [64] |
| Respiratory syncytial virus | Mice | - | Increased persistence of viruses and extended viral-specific gene expression were seen in CC16 deficient mice after RSV infection | [79] |
| Asthma | Human; Serum | ↓ | Mutation in CC16 gene increased risk of asthma in childhood CC16 levels decreased in asthmatic patients with a long duration of the disease compared to those with a short duration Significantly decreased in patients with refractory and non-refractory asthma |
[67,68,69,70] |
| Asthma | Human; Serum | No difference | No significant association between CC16 serum levels and asthma among athletes | [64] |
| Asthma | Human; Airways | ↓ | Fewer CC16 epithelial cells in the airways of asthmatic patients compared to controls Lower CC16 concentration in BALF of asthmatics compared with control healthy subjects |
[58,70,71] |
| Asthma | Human; Sputum | ↑ | Higher CC16 levels in sputum from patients with mild to moderate and refractory asthma compared to controls | [15,72] |
| Asthma | Human; urine | ↓ | Lower urine CC16 levels in asthmatics children compared to healthy children | [73] |
| Allergic rhinitis | Human; Serum | No difference | No significant association between CC16 serum levels and allergic rhinitis among athletes | [64] |
| Allergic rhinitis | Human; Sputum | No difference | No difference in CC16 levels between atopic rhinitis and non-atopic controls | [15] |
| Allergic rhinitis | Human; Nasal lavage fluids | ↓ | Reduction in the levels of CC16 in nasal lavage fluids compared with controls during the pollen season | [74,75] |
Abbreviations: CC16, Club cell secretory protein; ALI, Acute lung injury; ARDS, Acute respiratory distress syndrome; ↑, increase; ↓, decrease; BALF, Bronchoalveolar lavage fluid; BPD, Bronchopulmonary dysplasia; COPD, Chronic obstructive pulmonary disease; FEV1, Forced expiratory volume in one second; WT, Wild type; IPF, Idiopathic pulmonary fibrosis; PF, Pulmonary fibrosis; BAMSE, Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey; MAAS, Manchester asthma and allergy study; CRS, Children’s Respiratory Study; LHS, Lung Health Study; RSV, Respiratory syncytial virus; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; TESAOD, Tucson epidemiological study of airway obstructive disease; ECRHS, European community respiratory health survey; SAPALDIA, Study on air pollution and lung disease in adults.