The rapid advancement of flexible electronics has driven innovation in wearable respiratory monitoring devices, yet challenges remain in achieving medical-grade precision for quantitative pulmonary function assessment. This study integrates water molecule-responsive flexible sensing technology, wearable devices, and a cloud-based intelligent analysis platform to develop the first medical-grade flexible respiratory sensing system (SFMS). By leveraging the synergistic effect of bionic microcavity differential pressure sensing and humidity-sensitive interfaces, combined with a pressure difference-flux dynamic model, the system enables simultaneous resolution of peak expiratory flow (PEF) and forced vital capacity (FVC), accurately deriving core pulmonary function indicators such as FEV1/FVC. Clinical validation across 454 cases demonstrated high consistency with gold-standard spirometry (intraclass correlation coefficient [ICC] = 0.93–0.97), with 89.7% sensitivity and 92.3% specificity in differentiating chronic obstructive pulmonary disease (COPD) from asthma. Technologically, this work pioneers medical-grade flexible sensing for quantitative pulmonary testing, eliminating dependence on specialized operators through an embedded edge computing architecture that supports real-time cloud data interaction. The system establishes disease-specific profiles through multi-parametric physiological correlation analysis. Practically, its low cost, portability, and user-friendly operation facilitate seamless integration into primary healthcare and home health management, providing technical tools for hierarchical diagnosis and treatment of chronic respiratory diseases. Aligned with WHO's Respiratory Health Action Plan, this innovation enables universal monitoring to advance early screening and long-term disease management. With significant clinical translation potential, it offers a groundbreaking solution for building a comprehensive prevention and control framework for respiratory diseases.