Ambient air pollution's health impacts are well documented, yet the domestic environment remains underexplored. We aimed to compare indoor versus outdoor (I/O) air quality and estimate the association between indoor/ambient fine particulate matter (PM2.5) exposure and lung function in asthma and chronic obstructive pulmonary disease (COPD) patients. The study involved 24 h monitoring of PM2.5 levels indoors and outdoors, daily peak expiratory flow (PEF), and biweekly symptoms collection from five patients with asthma and COPD (average age of 50 years, 40% male) over a whole year. Data analysis was performed with linear mixed effect models for PEF and generalized estimating equations (GEE) for exacerbations. More than 5 million PM2.5 exposure and meteorological data were collected, demonstrating significant I/O PM2.5 ratio variability with an average ratio of 2.20 (±2.10). Identified indoor PM2.5 sources included tobacco use, open fireplaces, and cooking, resulting in average indoor PM2.5 concentrations of 63.89 μg/m3 (±68.41), significantly exceeding revised World Health Organization (WHO) guidelines. Analysis indicated a correlation between ambient PM2.5 levels and decreased PEF over 0-to-3-day lag, with autumn indoor exposure significantly impacting PEF and wheezing. The study underscores the need to incorporate domestic air quality into public health research and policy-making. A personalized approach is required depending on the living conditions, taking into account the exposure to particulate pollution.