Methotrexate is not suggested as a replacement for taking corticosteriods by mouth ("steroid sparing") due to the adverse effects associated with taking methotrexate and the minimal relief provided for asthma symptoms. Macrolide antibiotics, particularly the azalide macrolide azithromycin, are a recently added GINA-recommended treatment option for both eosinophilic and non-eosinophilic severe, refractory asthma based on azithromycins efficacy in reducing moderate and severe exacerbations combined. Azithromycins mechanism of action is not established, and could involve  pathogen- and/or host-directed anti-inflammatory activities. Limited clinical observations suggest that some patients with new-onset asthma and with "difficult-to-treat" asthma (including those with the asthma-COPD overlap syndrome - ACOS) may respond dramatically to azithromycin. However, these groups of asthma patients have not been studied in randomized treatment trials and patient selection needs to be carefully individualized.For children with asthma which is well-controlled on combination therapy of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA), the benefits and harms of stopping LABA and stepping down to ICS-only therapy are uncertain. In adults who have stable asthma while they are taking a combination of LABA and inhaled corticosteroids (ICS), stopping LABA may increase the risk of asthma exacerbations that require treatment with corticosteroids by mouth. Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life. Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalisation is uncertain.
Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well. The concept that "non-atopic" is synonymous with "non-allergic" is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex (P<0.0001), indicating that asthma is almost always associated with some sort of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of aeroallergens studied (the "missing antigen(s)" hypothesis). For example, an updated systematic review and meta-analysis of population-attributable risk (PAR) of Chlamydia pneumoniae biomarkers in chronic asthma found that the PAR for C. pneumoniae-specific IgE was 47%. Infectious asthma
When queried, asthma patients may report that their first asthma symptoms began after an acute lower respiratory tract illness. This type of history has been labelled the "infectious asthma" (IA) syndrome, or as "asthma associated with infection" (AAWI) to distinguish infection-associated asthma initiation from the well known association of respiratory infections with asthma exacerbations. Reported prevalences of IA for adults range from around 40% in a primary care practice to 70% in a specialty practice treating mainly severe asthma patients. The true population prevalence  of IA in adult-onset asthma is unknown because clinicians are not trained to elicit this type of history routinely, and recollection in child-onset asthma is challenging. Differential diagnosis
Many other conditions can cause symptoms similar to those of asthma.