# Diet and Asthma: A Narrative Review
## 2 Asthma Phenotypes and Endotypes  
Asthma is defined as \"(...) a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation.\" [2]. Episodes usually resolve either spontaneously or with medication [2; 6], but episodic flare-ups can still occur and be life-threatening, thereby holding a significant burden to the patient's life [2]. Even though genetic determinants play a role in the initiation of various asthma pathways, several research work have identified the role of environmental changes in the ongoing asthma epidemic [7]. This disease etiology is attributed to the interactions of environmental exposures, host factors, and genetic susceptibility. Environmental factors include weather, air pollution, molds, pollens, and other aeroallergens; host factors comprise obesity, diet and nutritional factors, allergic sensitization, and the susceptibility to infections; while genetic factors encompasses a large number of asthma susceptibility loci [1; 8]. Asthma has different phenotypes and endotypes [7; 9]. Consequently, there are variations in its clinical severity and treatment response, and these differences may reflect their pathobiological pathways [9]. Patients may respond very differently to the same therapeutic interventions despite having similar clinical symptoms [7; 9]. A long-standing clinical approach to asthma has been to categorize patients into phenotypes based on observable combinations of biological, clinical, and physiological characteristics [9]. However, the strategy to link molecular mechanisms to specific phenotypes has been evolving [9], and endotypes of asthma describe these distinct pathophys at the cellular and molecular levels [9]. The common description of asthma is one of excessive T-helper type 2 (Th-2) cell responses and specific immunoglobulin E (IgE) production, leading to allergic sensitization and airway hyperresponsiveness [9; 10]. However, the term \"asthma\" is now considered a heterogenous definition, representing a collection of several distinctly disordered pathways; when referring to endotypes, the more broadly used are type 2-high (T2H) and type 2-low (T2L) asthma [7; 9]. A visual representation of T2H and T2L asthma and the involved lymphocytes and cytokines are presented in Figure 1.  
T2H is characterized by airway eosinophil inflammation [9,11,12] that is stimulated by the adaptive, and, or the innate immune systems: Th-2 cells and type-2 innate lymphoid cells (ILC2s), respectively [7]. This response primarily releases the interleukin (IL) cytokines IL-4, IL-5, and IL-13, respectively [7,12]. IL-4 mediates the differentiation of T cells into Th2 cells [7], and also contributes to the production of IgE by B cells and mast cell degranulation [7,13]. IL-5 has a preponderant role in the recruitment, survival, and maturation of eosinophils [7,13], and IL-13 contributes to the hyperresponsiveness of airway smooth muscle cells and goblet cell hyperplasia [7]. The production of other mediators and chemokines by eosinophils further adds to tissue remodeling [7]. Type 2 immunological responses are linked to atopic diseases and allergy asthma [12]. T2L is sometimes referred in a simplistic way as non-eosinophilic asthma [11,14]. However, not much is known about the pathobiology of T2L asthma [7] other than it is mostly characterized by neutrophylic or paucigranulocitic inflammation [9,11,14], with the latter being defined as patients that do not present eosinophilic or neutrophylic airway inflammation [11,14] but have confirmed airway hyper-responsiveness (AHR) and experience persistent symptoms [11]. Within non-eosinophilic asthma, Th-1 and Th-17 pathways appear to be implicated in neutrophilic asthma [7,13].