Asthma

Asthma causes recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. Symptoms are usually worse at night and in the early morning or in response to exercise or cold air. Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms. ==Classification==

Due to the diversity in onset, symptoms, outcomes, and response to treatment, asthma is often considered a syndrome — a collection of signs and symptoms — rather than a single condition. Historically asthma was classified as being caused by external factors (extrinsic) such as allergens or by internal factors (intrinsic), unrelated to allergies. Asthma and chronic obstructive pulmonary disease (COPD) cause airway restriction and have a wide range of overlapping mechanisms and symptoms. The main difference between the two disorders is that in asthma expiratory airflow fluctuates over time while in COPD airflow obstruction is chronic and can increase in severity over time. Asthma is most commonly divided into two endotypes, T2-high and T2-low (non-T2). Within the two main endotypes there are subpopulations (phenotypes), some of which overlap or can be categorized under both of the two endotypes. ==Causes==

Asthma is caused by a mixture of genetic and external factors. The disease manifests when those with a genetic susceptibility to asthma are exposed to specific environmental factors. Environmental factors can also trigger asthma symptoms. Risk factors Factors during pregnancy that have been linked to the development of asthma include weight gain or obesity in the mother, stressful pregnancy, smoking while pregnant, the use of certain medications while pregnant and caesarean section. Early childhood exposure to secondhand smoke, high levels of stress in parents, respiratory infections, and indoor mold or fungi have also been associated with asthma development. Prenatal or childhood exposure to cigarette smoke increases the likelihood of a child developing asthma. Children whose maternal grandmother smoked during pregnancy are also more likely to develop asthma, regardless of if their mothers developed asthma or smoked. Nicotine is believed to be the cause of these effects and nicotine is linked to changes in DNA. Conversely, there has been research suggesting that certain infections during childhood may lessen the risk of developing asthma. This theory is known as the "hygiene hypothesis". Twin studies and family studies support a substantial heritable component, with estimates that roughly half or more of asthma susceptibility is explained by genetics Large genome-wide association studies (GWAS) and sequencing efforts indicate that risk reflects the cumulative effects of numerous common genetic variants together with a more limited contribution from rare variants, rather than a small number of loci of large effect. Meta-analyses now report over 200 genome-wide significant susceptibility loci, many mapping to immune and epithelial genes and explaining a measurable, though still incomplete, fraction of heritability. Pathway analyses consistently highlight type 2 inflammation, epithelial barrier function, and both innate and adaptive immune signalling, including loci near or within IL33, IL1RL1/IL18R1, TSLP, MHC class II, and GATA3. Multiple genes in this region, including ORMDL3 and GSDMB, appear to act primarily through regulatory mechanisms, with gene-environment interactions and age-dependent effects on airway epithelial responses, particularly to early-life viral infections. Consistent with this architecture, polygenic risk scores (PRS) derived from multi-ancestry GWAS can stratify individuals by asthma risk, with higher predictive performance for childhood-onset than adult-onset disease. Individuals in the highest PRS percentiles show several-fold increased odds of childhood asthma, and PRS analyses have helped delineate heterogeneity across asthma–COPD overlap and related comorbid traits, although clinical implementation remains investigational. Many asthma-associated variants act within regulatory elements, with effects that are highly cell-type specific and modulated by environmental exposures such as allergens, air pollution, and respiratory infections. Integrative genomic and epigenomic studies show enrichment of risk alleles in enhancers active in airway epithelial and immune cells, and indicate that DNA methylation and other epigenetic modifications mediate part of the gene-environment interaction underlying asthma susceptibility and phenotypic heterogeneity. Exacerbations Asthma exacerbations are commonly triggered by external factors or underusage of inhaled corticosteroid medications, however exacerbations can be sudden and unexplained. Triggers for asthma exacerbations include viral respiratory infections, exposure to allergens, food allergies, outdoor air pollution, season changes or back to school season in the fall, lack of adherence to inhaled corticosteroids, and epidemics of severe asthma exacerbations in a community. ==Pathophysiology==

The mechanisms underlying asthma and asthma symptoms include spasms in the bronchial muscles, inflammation in the airways, hypersensitive airways, and excessive secretion of mucus in the airways. In asthma, the airways contract more than what is normal in response to both internal and external triggers. This hyperresponsiveness alongside inflammation affects the nerves in the airways — making them more sensitive — and causes the body to produce too much mucus. Contraction of airway smooth muscle, swelling (edema), thickening of the airway wall due to remodelling, increased mucus production, and mucus plugs contribute to narrowing of the airways. Airway hyperresponsiveness is excessive narrowing of the airways in response to stimuli that are normally harmless. This narrowing leads to variable airflow restriction and asthma symptoms. Airway hyperresponsiveness is somewhat reversible with treatment. ==Diagnosis==

Asthma is defined by the Global Initiative for Asthma as: Spirometry is then used to confirm the diagnosis. It is the single best test for asthma.