The goal of this study is to learn how the body's immune system affects disease control in people with different airway inflammatory diseases.We want to understand:

1.Whether specific immune cell patterns in the blood are linked to how severe the disease is or how well it is controlled.

Participants will:

1. Answer questions about their health and symptoms.
2. Give blood samples
3. Have lung function tests and other standard check-ups.
4. share sleep study results. We will compare people with airway diseases to healthy volunteers to see how their immune systems differ.

This prospective, single-center observational cohort study aims to comprehensively characterize the immune landscape of patients with chronic airway inflammatory diseases through the application of high-dimensional single-cell technologies.The study plans to enroll approximately 205 to 215 participants, comprising multiple disease groups and matched healthy controls.

A core methodological innovation of this study is the use of CyTOF (Cytometry by Time-Of-Flight), a mass cytometry platform capable of simultaneously analyzing up to 40-100 immune markers at the single-cell level. This approach allows for a highly detailed phenotypic and functional profiling of peripheral blood mononuclear cells (PBMCs), enabling the discovery of disease-associated immune cell subsets with greater resolution than conventional flow cytometry.

Participants will be stratified by disease type and severity based on clinical diagnostic criteria, functional testing (e.g., FEV1, AHI, FeNO), and established clinical scores (e.g., ACQ, CAT, GOLD, SGRQ, E-FACED). Blood samples will be processed for PBMC isolation and subjected to CyTOF analysis. Complementary assessments include cytokine profiling via ELISA, single-cell RNA sequencing (scRNA-seq) for transcriptomic insights, and sputum analysis via culture and next-generation sequencing (NGS) to evaluate microbial colonization and inflammatory cell profiles.

This study will investigate the correlation between immune phenotypes and clinical control levels, disease severity, hypoxia metrics, and inflammatory mediators (e.g., IL-6, TNF-α). It also seeks to identify key immunopathological features that may differentiate subtypes within each disease (e.g., T2-high vs. T2-low asthma; Pseudomonas-positive vs. negative bronchiectasis) and evaluate transitional states such as PRISm in relation to COPD progression. Multivariate models combining immune and clinical parameters will be developed to facilitate predictive stratification and to guide future individualized immunotherapeutic strategies.

By integrating CyTOF, scRNA-seq, and clinical data, this protocol aspires to define immune biomarkers predictive of airway disease control and severity and to provide a systems-level understanding of immune dysfunction across heterogeneous respiratory disorders.

Inclusion Criteria

1. Age ≥18 years (≥40 years for COPD patients).
2. Clinical diagnosis of asthma, ABPA, bronchiectasis, OSAS, or COPD according to established criteria.
3. PRISm patients (post-BD FEV1/FVC ≥70% and FEV1 <80% predicted)
4. Smoking controls: ≥10 pack-years, normal lung function, no chronic respiratory symptoms.
5. Healthy controls: normal lung function, FeNO <20 ppb, total IgE <100 IU/mL, no chronic disease, smoking <10 pack-years, no immunosuppressant use within 3 months.

Exclusion Criteria

1. Patients with severe respiratory diseases other than those included in the study, such as pulmonary embolism, pneumothorax, pulmonary hypertension, interstitial lung disease, or active lung cancer.
2. Patients with severe systemic diseases that may interfere with study completion, such as myocardial infarction, severe arrhythmia, hepatic insufficiency, renal insufficiency, hematological disorders, or malignancy.
3. Patients with an acute exacerbation within 4 weeks before enrollment, or systemic use of antibiotics, antifungal drugs, immunosuppressive agents, cytotoxic agents, or corticosteroids (except for long-term maintenance therapy)
4. Pregnant or lactating women.
5. Patients with poor compliance as judged by the investigators.
6. Subjects currently participating in other clinical studies.

This study included patients diagnosed with airway inflammatory diseases who were treated at the First Affiliated Hospital of Ningbo University.