| Area | Study (first author year) | Population/Model & N | Key finding | Quantitative stats | Assay/Method | URL/DOI | Publication date |
|---|---|---|---|---|---|---|---|
| Asthma | Xu 2024 | Human plasma cohort: 20 asthma patients and 20 healthy controls; complementary HDM mouse models (pqac-00000008) | CC10/SCGB1A1 is lower in asthma and functionally suppresses allergic airway inflammation by modulating lung dendritic cells rather than directly inhibiting Th cells; linked to NF-κB signaling in DCs (pqac-00000008) | Human cohort sizes: n=20 asthma, n=20 controls; lower CC10 correlated with increased IgE and lymphocytes; excerpt did not provide p-values. In mice, Cc10−/− increased inflammatory infiltrates, Th2 cytokines, antigen-specific IgE and AHR; recombinant CC10 significantly attenuated responses (pqac-00000008) | ELISA in human plasma; HDM-induced allergic airway inflammation models; mixed lymphocyte response; DC phenotyping/mechanistic assays (pqac-00000008) | https://doi.org/10.1007/s00018-024-05368-z | Jul 2024 |
| ARDS | Gerard 2024 | Distal airway tissue: controls n=15, ARDS n=25; subset immunostaining ARDS n=13 vs controls n=11; serum/BALF ARDS n=24 vs controls n=7 (pqac-00000019, pqac-00000020, pqac-00000021) | ARDS causes major airway epithelial injury; tissue club-cell area by CC16/SCGB1A1 staining was not significantly changed, but serum CC16/SCGB1A1 increased, consistent with epithelial leak/spillover rather than club-cell expansion (pqac-00000020, pqac-00000030) | Epithelial denudation 20% [IQR 5–40] vs 0% [0–0], p=0.0003; neutrophilic infiltration p=0.0005; ciliated-cell loss: β-tubulin area 0.61% [0.25–1.0] vs 3.67% [1.09–5.76], p=0.0317; Fox-J1 area 20.4% [5.1–30.8] vs 32.2% [27.1–43.5], p=0.034; goblet-cell trend p=0.055; pIgR area 14.42% [7.82–22.87] vs 41.57% [38.49–49.21], p<0.0001; serum SC 599 pg/mL [413–952] vs 133 [103–137], p<0.0001; serum S-IgA1 71.4 μg/mL [49.9–117.4] vs 10.8 [4.08–13.6], p<0.0001; serum CC16/SCGB1A1 increased (numeric value not in excerpt) (pqac-00000019, pqac-00000020, pqac-00000021) | Histology, multiplex immunofluorescence, serum and BALF ELISA; figure review confirms CC16 panel and no significant tissue difference in Fig. 2d (pqac-00000020, pqac-00000030) | https://doi.org/10.1186/s13054-024-05127-3 | Oct 2024 |
| Occupational exposure | Neumann 2024 | Potash miners/workers: initial cohort 689 employees, 672 with paired CC16 values; facility n=97, maintenance n=97, mining n=478 (pqac-00000011, pqac-00000017, pqac-00000018) | Serum CC16/SCGB1A1 is a small-airway epithelial effect marker, but interpretation is strongly affected by circadian rhythm, smoking, and renal function; work-exposure effects were evident mainly in current smokers (pqac-00000011, pqac-00000016, pqac-00000018) | Median serum CC16: pre-early shift 10.15 ng/mL [3.65–26.00] vs post-early shift 15.30 [4.60–29.70], p=0.0005; pre-midday shift 13.80 [5.20–34.80] vs post-midday shift 10.70 [3.40–28.10], p<0.0001. Age correlated with CC16 pre-shift rS=0.14, p=0.0003; post-shift rS=0.13, p=0.0006. In never smokers, post-shift creatinine vs CC16 shift-difference rS=-0.15, p=0.0183. In underground current smokers, post-shift creatinine correlations with CC16 shift-difference: maintenance rS=-0.26, p=0.0096; mining rS=-0.10, p=0.0262. No significant exposure effects in never smokers; significant negative exposure correlations in current smokers (pqac-00000016, pqac-00000017, pqac-00000018) | Personal exposure monitoring (NO, NO2, CO, EC-DPM), paired pre/post-shift serum CC16, creatinine, Spearman correlations, multiple linear regression (pqac-00000011, pqac-00000016, pqac-00000018) | https://doi.org/10.1007/s00420-023-02035-x | Dec 2024 |
| Airway remodeling scRNA-seq | Cao 2024 | Air-liquid interface human bronchial epithelial cultures from healthy nonsmokers and COPD smokers; total 41,215 single cells across 6 groups (healthy 7,563; healthy+ECE 5,121; healthy+CSE 6,588; COPD 7,185; COPD+ECE 7,560; COPD+CSE 7,198) (pqac-00000015) | SCGB1A1 marks club and secretory-club populations; e-cigarette vapor and cigarette smoke alter club/ciliated differentiation, with Notch signaling implicated in e-cigarette-induced remodeling and reduced SCGB1A1 protein as an injury marker (pqac-00000014, pqac-00000015) | Club-cell fraction increased from 10% to 17% (ECE) or 21% (CSE) in healthy cultures; from 9% to 22% (ECE) or 27% (CSE) in COPD cultures. Ciliated4 fraction decreased with CSE from 7.2% to 2.4% in healthy cultures and from 4.3% to 1.9% in COPD cultures. ECE caused a differentiation state intermediate between untreated and CSE-treated cells; article reports decreased SCGB1A1 protein in e-cigarette users but snippet gives no p-value (pqac-00000014, pqac-00000015) | scRNA-seq, UMAP, pseudotime/velocity analysis, immunostaining, qPCR, ELISA; exposure at equal nicotine concentration 0.02 mg/mL (pqac-00000014, pqac-00000015) | https://doi.org/10.1186/s12931-024-02962-4 | Sep 2024 |
| COPD / club-cell heterogeneity | Blackburn 2023 | Review integrating human scRNA-seq, ALI culture, microscopy, and lineage/progenitor studies (pqac-00000022, pqac-00000024, pqac-00000026, pqac-00000027) | 2023 view: SCGB1A1 is the canonical human club-cell marker, but club cells are heterogeneous and lie on basal–club–goblet/alveolar continuums; smokers/COPD show loss of SCGB1A1+ club/secretory populations and impaired differentiation of basal cells into SCGB1A1+ cells (pqac-00000022, pqac-00000024, pqac-00000027) | SCGB1A1+ cells comprise ~11% of terminal bronchiolar cells and ~22% of respiratory bronchiolar cells. Highly purified human KRT5+SCGB1A1− basal cells were 99.0 ± 1.1% pure and could generate SCGB1A1+ cells in ALI culture. In humans, 11–44% of proliferating airway cells can be Scgb1a1+ and up to 25% of goblet cells express SCGB1A1. Quantitative COPD effect sizes not provided in excerpts, but multiple studies cited lower SCGB1A1 protein/mRNA and fewer SCGB1A1+ cells in smokers/COPD (pqac-00000022, pqac-00000024, pqac-00000026, pqac-00000027) | Review of scRNA-seq/trajectory analyses, ALI differentiation studies, immunostaining, lineage/progenitor studies (pqac-00000022, pqac-00000024, pqac-00000026, pqac-00000027) | https://doi.org/10.1152/ajplung.00192.2022 | May 2023 |
| Biomarker biology / translational overview | Otelea 2023 | Review of occupational/interstitial lung disease relevance and club-cell biomarker biology (pqac-00000012, pqac-00000013) | CC16/SCGB1A1 is a rapidly cleared circulating biomarker of club-cell/epithelial injury with practical relevance for exposure-related lung damage, but timing and renal handling matter (pqac-00000012, pqac-00000013) | Club cells comprise ~11–22% of respiratory bronchiolar cells; CCSP/CC16 is a 70-aa homodimer of 15,840 Da; healthy nonsmokers: ~1–5 μg/mL in BALF and ~10–15 ng/mL in plasma; plasma half-life in ARDS <18 min. Review also cites workers with VGDF exposure having 2.64% more high-attenuation CT areas (95% CI 1.23–4.19%) vs non-exposed (pqac-00000012, pqac-00000013) | Review synthesis of biomarker, exposure, and pathology studies (pqac-00000012, pqac-00000013) | https://doi.org/10.3390/biomedicines12010078 | Dec 2023 |
| Mechanistic overview | Martinu 2023 | Authoritative review of human and model-system CCSP/SCGB1A1 biology (pqac-00000000, pqac-00000005, pqac-00000010) | SCGB1A1 is a major secreted club-cell product and negative regulator of lung inflammation; proposed mechanisms include IL-8 binding, VLA-4 interaction, PLA2 antagonism, and modulation of dendritic-cell/Th17 and fibronectin-IgA pathways (pqac-00000000, pqac-00000010) | CCSP described as ~16-kDa secreted protein and among the most abundant lung proteins; circulating levels rise from birth to adulthood, are reduced by smoking/chronic exposures, and acutely increase after epithelial injury; excerpt provides no OR/AUC/p-values (pqac-00000000, pqac-00000005, pqac-00000010) | Review of human, animal, and mechanistic studies (pqac-00000000, pqac-00000005, pqac-00000010) | https://doi.org/10.1146/annurev-med-042921-123443 | Jan 2023 |


*Table: This table summarizes the main quantitative and mechanistic findings on human SCGB1A1/CC10/CC16/CCSP from the evidence collected, emphasizing recent 2023-2024 studies. It is useful for comparing how SCGB1A1 behaves across asthma, ARDS, occupational exposure, airway remodeling, and COPD-related club-cell biology.*