Asthma causes the airways of the lungs to swell and narrow, leading to wheezing, shortness of breath, chest tightness, and coughing.

It is distinguished by bronchial hyper-responsiveness, which is an exaggerated response of the airway characterized by swelling (edema) and infiltration of inflammatory immune cells.

Allergens and inflammatory cytokines are typical culprits involved in triggering asthmatic attacks (Morris 2012). Asthma symptoms include wheezing, chest tightness, shortness of breath, and coughing. The disease affects people of all ages, but often begins during childhood. In the United States, more than 22 million people have asthma.

Asthma therapies aim to reduce this inflammation and improve airway function. Conventional treatment modalities can effectively treat asthma in many cases; but for those with chronic, severe asthma, long-term use of glucocorticoids is linked to detrimental side effects like bone fractures and adrenal dysfunction (Vestergaard 2007; Pauwels 1998).

An underutilized tool in the battle against asthma is blood testing for environmental and food allergens and for less conspicuous food sensitivities that may trigger inflammation. When potential triggers have been identified, many asthma patients may be able to improve their quality of life by avoiding exposures or eliminating foods to which their immune system is highly reactive (Young 2011; Wang 2005; Lee 2011; Shakib 1986).

In this protocol, you will learn what causes asthma and how lifestyle and dietary choices can mitigate asthma exacerbations. You will also learn which medical treatments can help relieve symptoms and discover that emerging drug strategies appear promising. Lastly, you will read about several natural compounds that may complement conventional treatment strategies and target asthmatic inflammation from multiple angles.

Airway inflammation. In those with asthma, cells and tissues within the airway are prone to inflammatory reactions against normally harmless substances. This inflammation can cause swelling, mucous production and lead to airway narrowing (Lemanske 2010). Airway narrowing. Airway narrowing gives rise to asthma symptoms. When the airways are exposed to substances that trigger a reaction, immunoglobulin E (IgE) antibodies produced by B-cells help facilitate the release of inflammatory mediators including histamine and leukotrienes from mast cells. These mediators cause the airway smooth muscles to contract or spasm, triggering airway narrowing (i.e., bronchoconstriction). Sensory nerves in the muscles become more sensitized, contributing to more bronchospasms (Miller 2001).

Airway remodeling. Structural changes in bronchial tubes can occur with chronic and uncontrolled asthma attacks. For instance, epithelial cells (the layer of cells that line the airways and function as a barrier) can shed, allowing irritants or allergens to further penetrate into the inner muscle cells (James 2005; Davies 2009; Campbell 1997). Sensory nerves can also become exposed leading to reflex neural effects on the airways (Kaufman 2011).

Allergies and sensitivities. Allergies underlie many cases of asthma. An allergy is an inappropriate immune response against an innocuous compound. A wide variety of environmental allergens can cause an asthma attack (Young 2011), including food allergies (Wang 2011).

For those whose asthma is associated with environmental allergies, immunotherapy (e.g., “allergy shots” or sublingual immunotherapy) may help prevent exacerbations (Abramson 2003; Morris 2012, Fujimura 2012).

In the case of food sensitivities, experimental research suggests that chronic, low-level inflammatory reactions triggered by an immune response to food particles may set the stage for airway inflammation (Lee 2011; Shakib 1986). Those with asthma would be wise to test to see if they are producing high levels of IgG antibodies towards any particular food(s). Some evidence suggests that IgG antibody testing is able to detect immune reactions less severe than an overt allergy, but that nonetheless may trigger inflammation (Lee 2011; Shakib 1986; Oehling 1984).

More information about the role of allergies and sensitivities in triggering inflammatory reactions throughout the body is available in the Allergies protocol.

Tobacco smoke. Studies have consistently shown a relationship between smoking and asthma. Smoking is also related to decreased asthma control, higher risk of asthma attacks, and death. Improvements in lung function and asthma symptoms have been observed among those who quit smoking (Stapleton 2011).

Occupational exposure. Occupations commonly associated with asthma include woodworking, detergent manufacturing, some health care professions, and baking (PubMed Health 2011; Bakerly 2008; Vandenplas 2011).

Infections. A variety of common viral infections acquired during infancy and early childhood appear to increase the risk of childhood wheezing episodes that may eventually lead to asthma (Lemanske 2010). In contrast, other evidence suggests that childhood exposure to microbial pathogens and foreign peptides may protect against the development of childhood asthma – a theory known as the hygiene hypothesis (Murk 2011; Mannie 2010).

Medications. Certain medications, including non-steroidal anti-inflammatory drugs (NSAIDs) and ACE-inhibitors, can trigger an asthma attack in some people (Sanfiorenzo 2011).

Exercise.Exercise can trigger asthma exacerbations, so people with asthma should exercise with caution (NHLBI guidelines).

A comprehensive assessment is needed to differentiate between asthma versus an alternate disease or condition such as emphysema, early congestive heart failure or vocal cord problems.. The physician makes a clinical diagnosis based upon symptoms, severity, and results from lung/respiratory function tests. (Morris 2012). To make a thorough assessment and help the patient manage the disease, the physician obtains a detailed medical history.

Lung & Airway Function Tests Spirometry. Spirometry is the recommended method for diagnosing asthma. It measures the degree and severity of airflow obstruction by assessing the rate and amount of air expelled after taking a deep breath (Pearce 2011).

Peak Flow Meter. The peak flow meter measures the maximum speed of air from forced expiration, known as peak expiratory flow (PEF). It measures the airflow through the bronchi and thus the degree of obstruction in the airways. This simple test can also be used to monitor asthma conditions in the home (Kaufman 2011).

Asthma is treated pharmacologically in a stepwise fashion depending on severity of symptoms. Asthma medications include quick-relief medications used to treat acute symptoms of an asthma attack and long-term control medications used to prevent further exacerbations. The goal of treatment is to optimize long-term control so that quick-relief medications, which have many side effects, can be minimized or eliminated (Simons 1999).

Quick-relief medications

Short-acting beta-2 agonists (SABAs).SABAs cause bronchodilation of the smooth muscles of the airway. These drugs relieve breathlessness, chest tightness, and other acute symptoms of an asthma attack. SABAs are usually prescribed together with a maintenance medication. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Side effects of bronchodilators include rapid heart rate, increased blood pressure, increased blood sugar levels, irregular heart rhythms, and a variety of other responses (Wraight 2004). SABA medications include albuterol, levalbuterol, pirbuterol, bronkosol, isoproterenol, metaproterenol, and terbutaline. Use of SABA > 2 days a week for symptom relief generally indicates inadequate control and the need to step up treatment (see Stepwise Asthma Management; below).

Corticosteroids. Corticosteroids exert an immune-suppressing (i.e., anti-inflammatory) effect and can be administered systemically for a short course in acute or severe asthma to ease airway inflammation (Ohta 2011; Spahn 2008). However, systemic corticosteroids can lead to significant side effects including edema, osteoporosis, muscle weakness, chemical-induced diabetes, hypertension, adrenal gland dysfunction, cataracts, and glaucoma. They can also reduce calcium absorption from the gut and increase calcium loss from the kidneys (Pauwels 1998). To reduce the risk of these serious complications, the lowest dose possible should be taken to provide symptomatic control (Kaufman 2011).

Theophylline. Theophylline is a bronchodilator with modest anti-inflammatory properties. It can be used as an alternative stand-alone therapy for children older than 5 with persistent mild asthma. However, the toxic dose only slightly exceeds the effective dose, so patients must be carefully monitored (Wood 2009). Adverse effects include gastrointestinal symptoms, irregular heartbeat, seizures, and death (GINA 2011).

Inhaled anticholinergics. The neurotransmitter acetylcholine contributes to bronchoconstriction. Therefore, blocking the binding of acetylcholine to its receptors in the airways with inhaled anticholinergics inhibits this action. Anticholinergic medications are sometimes added to SABAs and help promote bronchodilation during an acute exacerbation (Ohta 2011).

Long-term control medications

Corticosteroids. Patients with asthma may require long-term use of inhaled corticosteroids (Ohta 2011; Spahn 2008). Potential adverse local effects associated with inhaled corticosteroids include thrush, hoarseness, reflex cough, and bronchospasm (GINA 2011). Long-term use of high-dose inhaled corticosteroids is associated with osteoporosis and adrenal dysfunction (Pauwels 1998). Commonly used inhaled corticosteroids include beclomethasone, budenoside, and triamcinolone.

Long-acting beta-2 agonists (LABAs). LABAs relax the airways and can provide up to 12 hours of bronchodilation (Wood 2009). They can be an add-on to long-term treatment for asthma that cannot be adequately controlled with inhaled corticosteroids alone. LABAs should not be used as stand-alone maintenance medications or to treat acute symptoms. The use of LABAs should be stopped if there is no response and the dose of inhaled corticosteroid is increased (Kaufman 2011). Studies have shown that LABAs can increase the risk of severe asthma attacks, asthma-related hospitalizations and death (GINA 2011). LABAs include salmeterol xinafoate and formoterol fumarate.

Leukotriene modifiers. Leukotriene receptor antagonists (blockers) and inhibitors of leukotriene synthesis help prevent or reduce inflammation, mucus production, swelling, and airway tightening. They are less effective than inhaled corticosteroids and thus are commonly used as an add-on therapy for poorly controlled, persistent asthma and exercise-induced asthma (Kupczyk 2011). Commonly used leukotriene modifiers include montelukast, zafirlukast and zileuton.

Mast cell stabilizers. Mast cell stabilizers (e.g., cromolyn and nedrocromil) prevent mast cells (a type of immune cell) from releasing histamine and related inflammatory mediators. These medications are very useful for preventing exercise-induced asthma when used prophylactically, but are not effective in treating an acute asthma attack. Mast cell stabilizers are also very safe but must be taken on a regular basis, even when free of symptoms (Merk Manual 2011).

Suplatast tosilate. The immunological reaction to antigens is driven by two counterbalancing paradigms – Th1 and Th2. In asthma, an imbalance favoring Th2 is observed (Nagai 2012). Suplatast tosilate is a Th2 cytokine inhibitor that has been shown to ease inflammation in asthma and related allergic conditions (Wada 2009; Stokes 2004). Clinical trials with suplatast tosilate have been quite promising. Not only has suplatast tosilate been shown to be at least as effective as some traditional asthma drugs (Shiga 2011), but it also improved lung function in asthmatic subjects who were already being treated with steroids (Tamaoki 2000; Sano 2003) as well as subjects who did not respond to leukotriene receptor antagonists (Wada 2009). Unfortunately, suplatast tosilate is not approved in the United States, but is available in Japan as Tosilart® and IPD Capsules® (Drugs.com 2012).

Biological Agents

Biological agents (biologics) are protein-based products, which include antibodies and recombinant protein-based receptors. Examples include humanized monoclonal antibodies (antibodies manufactured in the laboratory from identical immune cells), which target specific antibodies or cytokines.

Omalizumab (Xolair®). Omalizumab, a monoclonal antibody that inhibits a key mediator of antigen sensitization called immunoglobulin E (IgE), is approved to treat asthma. Omalizumab's cost is high and hence is mainly prescribed for patients with severe, persistent asthma, which cannot be controlled even with high doses of corticosteroids. Adverse effects of omalizumab include severe allergic reactions and cancer (Davydov 2005).

Monoclonal antibodies that target eosinophils. Eosinophils are immune cells that accumulate in sites of asthmatic inflammation and release inflammatory mediators (Walsh 2010; Conroy 2001). Interleukin-5 (IL-5) is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior (Corren 2011). Several humanized monoclonal antibody therapies (e.g., mepolizumab, benralizumab and reslizumab) have selected IL-5 as a potential target to prevent eosinophil-mediated inflammation in patients with asthma (Thomson 2011). In one placebo-controlled trial, mepolizumab was associated with significantly fewer severe exacerbations of eosinophilic asthma than placebo over the course of 50 weeks (Haldar 2009). Mepolizumab also significantly reduced the number of eosinophils in blood and sputum (Haldar 2009; Nair 2009). Another randomized, placebo-controlled trial found that intravenous infusions of reslizumab on poorly controlled eosinophilic asthma were generally well tolerated and reduced sputum eosinophil concentration, improved airway function, and trended toward greater asthma control compared to placebo (Castro 2011).

Pitrakinra (Aerovant®). Interleukin-4 (IL-4) is another important contributor to eosinophil-mediated inflammation (Piehler 2011). In two independent randomized, double-blind, placebo-controlled trials using a drug called pitrakinra (Aerovant®) that blocks the effects of IL-4, researchers were able to significantly relieve asthma symptoms in 28 subjects with allergic asthma compared to 28 subjects who received a placebo (Wenzel 2007).

Bronchial Thermoplasty

Bronchial thermoplasty is a therapy in which radio-frequency energy bursts are used to heat and destroy muscle tissue in the airway, thus hindering the ability of the bronchial tubes to constrict. It is used only for patients with severe refractory asthma. Results from clinical trials have shown that patients who underwent this procedure experienced fewer symptoms, enjoyed better quality of life and needed less emergency room visits (Gildea 2011).

Although bronchial thermoplasty is relatively safe, patients have to be monitored during (for symptoms of asthma and other adverse events) and after treatment because exacerbations can occur up to 6 weeks following the final procedure. The U.S. Food and Drug Administration has approved bronchial thermoplasty for treatment of severe refractory asthma but a follow up of the Phase 4 trial study participants to determine long-term effects of the procedure is still pending (Gildea 2011).

Asthma needs to be managed even when symptoms are not present. According to the 2007 guidelines issued by the National Heart, Lung and Blood Institute (NHLBI 2007), people with asthma should educate themselves and have a clear action plan (regardless of severity) for the management of their asthma symptoms.

To effectively control and manage asthma in the long-term, patients must be able to self-monitor their symptoms and recognize the warning sign(s) of an attack. They must also be able to respond quickly through timely use of medication(s) and/or other intervention(s). In addition, the patient must recognize and minimize contact with the specific asthma trigger(s) as well as manage other medical/health conditions that can exacerbate symptoms.

Managing Asthma Triggers

People with persistent or seasonal asthma as well as a family history of allergies should have testing for airborne and food allergens. Because asthma and allergies frequently co-exist, treating the allergy symptoms may improve asthma (Boulet 2011). If possible, patients should reduce their exposure to known allergens at home, school, work, or daycare. The patient’s allergist can suggest specific ways to remove the offending allergen(s) and keep the area(s) allergy-free. More information is available in the Allergies protocol.

Patients with asthma are advised to exercise with caution because it can trigger an attack (NHLBI guidelines). They are also advised to avoid exertion when the level of air pollution is high as it can exacerbate exercise-induced asthma. Studies have shown, however, that supervised exercise and leisure-time physical activity reduced symptoms and improved the quality of life in some people with asthma (Kosti 2012). Brief warm-ups and use of short-acting beta-2 agonist medications before exercise or vigorous activity may help prevent or alleviate asthma (Wood 2009).

Preliminary evidence shows that yoga and breathing exercises may also help manage asthma. However, more rigorous trials are needed to validate the evidence (Vempati 2009; Mekonnen 2010).

Managing Conditions Associated with Asthma

Treating conditions associated with asthma can help a patient manage and control the disease. Some evidence suggests that treating GERD may reduce asthma exacerbations and improve the quality of life for some asthma patients (Littner 2005). More information is available in the GERD protocol.

Proper rest and stress management are also important in reducing asthma attacks. Persistent asthma, especially if uncontrolled and severe, can bring about worry and anxiety in the patient. Likewise, evidence indicates that stress in general can precipitate and increase the risk of asthma attacks in children and adults (Wright 2011). More information is available in the Stress Management protocol.

Dietary Considerations

It has been observed that people (regardless of health state) who eat fewer fruits and vegetables have weaker lungs. Also, asthma patients who ate less fruits and vegetables had more frequent attacks (Gilliland 2003).

Obesity is also associated with asthma (Boulet 2011). Obese asthma patients who lost weight observed improvements in their respiratory symptoms and lung function (Maniscalco 2008).

Also, evidence has revealed that a healthy, antioxidant rich diet may be protective against asthma. For instance, three studies found that children who followed a strictly Mediterranean diet (emphasizing plant-based foods such as fruits, vegetables, whole grains, legumes and nuts, with limited intake of red meat) had lower risk of wheezing, diagnosis of asthma, and allergic rhinitis (Chatzi 2009; Arvaniti 2011; Grigoropoulou 2011). Adults who consumed Mediterranean style foods were also seen to have improved control over asthma symptoms (Barros 2008). Also, apples may be protective against asthma. Several population studies have found that greater consumption of apples is associated with lower asthma incidence; polyphenols and other compounds present in apples are thought to convey the protection (Boyer 2004; Hyson 2011).

Vitamin D

Vitamin D plays a crucial role in regulating a broad range of immune processes and anti-inflammatory reactions involved in asthma. Laboratory evidence from several animal models of allergic asthma suggest that vitamin D may play a role in reversing airway remodeling or airway inflammation in the asthmatic lung (Taher 2008; Damera 2009). Evidence also suggests that vitamin D may protect against asthma exacerbations (Majak 2011). Studies among asthma patients found that low or deficient blood levels of vitamin D were associated with several indicators of asthma (Chinellato 2011; Sutherland 2010; Searing 2010).

Observational studies have shown that pregnant women with higher intakes of vitamin D had children with lower risks of wheezing and asthma compared to women with lower intakes of prenatal vitamin D (Devereux 2007; Erkkola 2009; Miyake 2010a). Also, a longitudinal study on children with mild to moderate persistent asthma showed that low vitamin D levels were associated with higher risk of severe asthma exacerbations over a 4-year period (Brehm 2010). Another study found that children who have low vitamin D levels at age 6 are more likely to have asthma at age 14 compared to children with higher vitamin D levels (Hollams 2011).

In order to establish causality, intervention studies registered with the National Institutes of Health (clinicaltrials.gov) are underway to assess the ability of vitamin D to prevent or reduce the risk of asthma. Two randomized controlled clinical trials are ongoing to determine if maternal vitamin D supplementation can prevent childhood asthma (NCT00920621; NCT00856947). A clinical trial on adolescents and adults with asthma will test whether vitamin D supplementation affects the time of the first upper respiratory infection or severe exacerbation (NCT00978315). Another clinical trial on adults will test the effect of adding vitamin D to low-dose controller medications to prevent asthma symptoms and attacks (NCT01248065).

Vitamin E

A number of studies have suggested that consuming antioxidants such as vitamins C, E, flavonoids, and selenium, among others reduces the bronchoconstriction associated with asthma.

Vitamin E is a collective name for a group of four tocopherols and four tocotrienols, which possess antioxidant and anti-inflammatory properties. Studies have shown that vitamin E prevents the release of inflammatory cytokines, and specifically inhibits gene expression of IL-4 (Li-Weber 2002).

Studies have shown that asthma patients with higher vitamin E intakes had lower prevalence of wheezing, cough and shortness of breath compared to those with lower intakes (Litonjua 2012). Some studies also report that low maternal vitamin E intake is associated with an increased risk of wheezing in infants and children

(Miyake 2010b; Litonjua 2006), reduced lung function and increased risk of asthma in children 5 years old (Devereux 2006). While one formal review of studies confirmed the protective effect of maternal vitamin E intake on wheezing (Nurmatov 2011), another did not find evidence for an association between dietary intake of vitamin E and the risk of asthma (Gao 2008).

Vitamin C

Population based and experimental studies provide evidence for the link between low levels of vitamin C and asthma. An animal model has shown that supplementing with high-dose vitamin C at the time of allergy challenge decreased airway hyper-reactivity and lowered the number of inflammatory cells (Jeong 2010).

One randomized controlled trial demonstrated the role of antioxidants in asthma. Children with persistent asthma who were supplemented with omega-3 fatty acids, vitamin C, or zinc experienced improved lung function. When children received all three nutrients their lung function improved to an even greater extent than it did with the individual nutrients (Biltagi 2009). Another clinical trial of eight asthmatic subjects found that those given 1,500 mg of vitamin C daily for two weeks experienced significantly improved asthma symptom scores compared to subjects receiving placebo (Tecklenburg 2007).

Polyunsaturated Fatty Acids

The two main groups of polyunsaturated fatty acids (PUFAs) include omega-3’s and omega-6’s. Typical sources of omega-3 fatty acids include fish oil, leafy green vegetables, nuts, and flaxseeds. Primary food sources of omega-6 fatty acids include vegetable oils like corn and sunflower oils, and nuts.

The Western diet has seen a decrease in consumption of foods rich in anti-inflammatory omega-3 fatty acids and an increase in pro-inflammatory omega-6 fatty acids, a trend that may have contributed to a rise in asthma and allergic diseases (Black 1997). Observational studies report that higher intake of fish oil may be associated with lower risk of asthma (Laerum 2007; Miyamoto 2007), while higher intake of margarine was associated with asthma (Nagel 2005). Intervention studies also reported a potential benefit for the use of fish oil and omega-3 fatty acid supplements for asthma (Mickleborough 2006; Schubert 2009).

Probiotics

Evidence suggests that supplementation with beneficial bacteria – probiotics – may modulate components of the immune response and inflammatory processes (Feleszko 2007; Lomax 2009). Therefore, as asthma and allergy are intrinsically tied to inflammation, scientists have been interested in studying the effects of probiotics in people with asthma or other allergic diseases.

Probiotics have reliably shown positive effects in allergic rhinitis – a condition with allergic inflammation, similar to asthma. However, a clear therapeutic role of probiotics in adults with asthma needs to be further elucidated (Vliagoftis 2008). Although, probiotics have been shown to be effective among children with asthma (Chen 2010).

Selenium

Studies have shown that people with chronic or severe asthma may suffer from a selenium deficiency (Qujeq 2003; Allam 2004; Rubin 2004). Several studies have examined the use of selenium supplementation in asthma. One study found a decrease in corticosteroid use when patients were supplemented with 200 mcg daily (Gazdik 2002), while another study found significant clinical improvement with 100 mcg daily (Allam 2004). A 2007 study of 26 selenium deficient, asthmatic patients revealed improvements in asthma-related quality of life and lung function measurements when deficiency was corrected with 200 mcg of selenium daily for 16 weeks (Voicekovska 2007). Another randomized controlled study revealed improvements in quality of life with no change in objective lung function measures (Shaheen 2007).

Zinc

Large studies found that higher maternal intakes of zinc during pregnancy may protect against childhood wheezing and asthma (Litonjua 2006; Devereux 2006). Another study demonstrated that low levels of zinc in the sputum were associated with more episodes of wheezing, severe asthma and decreased lung function (Jayaram 2011). Also, a study found that allergic mice exposed to cockroach allergen and supplemented with zinc had significantly lower cytokines in their airways, lower blood IgE levels, and decreased airway hyper-responsiveness (Morgan 2011).

Magnesium

Laboratory studies indicate that magnesium can relax bronchial smooth muscles. (Gourgoulianis 2001).

In a randomized, placebo-controlled trial, patients with mild to moderate asthma who received 340 mg of magnesium daily for 6.5 months were found to have significantly lower bronchial reactivity, improved lung function, better asthma control and quality of life compared to the placebo group (Kazaks 2010). Two other trials among children with mild to moderate persistent asthma found similar benefits with magnesium supplementation (Bede 2003; Gontijo-Amaral 2007).

A recent comprehensive review of 16 clinical trials confirmed the benefit and safety of using intravenous magnesium sulfate in severe exacerbations (Song 2012).

Curcumin

Curcumin, a yellow pigment in the spice turmeric (found in curry powder), inhibits nuclear factor kappa-B (Nf-kB), a protein involved in the production of inflammatory cytokines (Oh 2011). This was demonstrated in a laboratory animal model of asthma where treatment with curcumin reduced airway hyper-responsiveness, prevented the activation of Nf-kB, and reduced the number of leukocytes (white blood cells) in lung fluid (Oh 2011).

Lycopene

Researchers looking at the effects of lycopene (the red pigment found in tomatoes and some fruits) on asthma patients found that more than half of the patients supplemented with lycopene were significantly protected from exercise-induced asthma (Neuman 2000). In animal models, lycopene supplementation suppressed the release of cytokines associated with the allergic response, suppressed the influx of eosinophils and mucus-secreting cells into the lung tissue and airways (Hazlewood 2011), and suppressed airway hyper-responsiveness and inflammatory mediators (Lee 2008).

Flavonoids

Flavonoids are polyphenols (found in fruits, vegetables, red wine, and tea) that have antioxidant and anti-inflammatory properties. Flavonoids have been associated with improved lung function (Garcia 2005). The following flavonoids/ flavonoid-containing plants have been studied in the context of asthma:

• Quercetin. Part of quercetin’s chemical structure is similar to cromolyn, a mast cell stabilizer sometimes used to treat asthma (Weng 2012). In one study, a high dietary intake of the flavonoids quercetin (found in wine, tea, and onions), naringenin (found in oranges and grapefruit), and hesperetin (found in oranges and lemons) was associated with a lower prevalence of asthma (Knekt 2002). Several animal models of asthma have demonstrated the anti-inflammatory properties of quercetin. In one study, a single-dose oral administration of quercetin caused significant broncodilation, both in culture and in vivo (Joskova 2011). In another study, oral administration of quercetin significantly reduced levels of the inflammatory cytokines IL-5 and IL-4 as well as inhibited mucus production in the lungs (Rogerio 2010). In yet another animal model, quercetin significantly inhibited all asthmatic reactions when it was administered before an asthma-inducing substance (Park 2009).
• Proanthocyanidin. Proanthocyanidin is the main constituent of Pycnogenol®, an extract from the French maritime pine bark. Proanthocyanidin is a powerful antioxidant that neutralizes free radicals (Cos 2004). A randomized, placebo-controlled trial found that children with mild to moderate asthma who received Pycnogenol® for 4 weeks in addition to daily and/or rescue inhalers had significantly improved lung function and asthma symptoms compared to the placebo group. Also, the treatment group was able to reduce or discontinue use of rescue medication(s) more often than the control group (Lau 2004). Similar results were found in a more recent trial among adults with stable, controlled asthma who used Pycnogenol® as an adjunct compared to inhaled corticosteroid only or placebo (Belcaro 2011).
• Ginkgo biloba. A flavonoid-rich extract of leaves of the Ginkgo biloba tree appears to be an effective asthma therapy (Mahmoud 2000; Li 1997; Tang 2007). In one study, ginkgo biloba extract was added to corticosteroids for 2 weeks. Researchers found that the sputum of patients on the ginkgo therapy had significantly less inflammatory cells compared to the drug-only or placebo groups, suggesting that ginkgo extract may relieve the airway inflammation associated with asthma (Tang 2007). In an animal model of asthma where an allergy challenge was followed by treatment with ginkgo, the extract inhibited the release of eosinophils in the lung tissue and mucus-secreting cells in the airways (Chu 2011).

Butterbur

Butterbur (Petasites hybridus) is a perennial shrub used since ancient times to treat a variety of conditions. Four substances - petasin, isopetasin, S-petasin and S-isopetasin - isolated from the plant can inhibit leukotrienes (inflammatory mediators associated with asthma) (Thomet 2002).

A few research teams have examined butterbur’s effectiveness for asthma with encouraging results. In one open label trial of 64 adults and 16 children and adolescents, asthma patients were treated for two months with butterbur extract, followed by an optional two-month treatment period. Data showed that all the measured symptoms improved throughout the study, and 40% of patients were able to reduce their intake of traditional asthma medications (Danesch 2004). Another study found that butterbur therapy, in conjunction with inhaled corticosteroids, reduced asthma symptoms (Lee 2004).

Results from a laboratory animal model showed potential for S-petasin as a therapeutic agent for asthma. S-petasin, administered under the skin of allergen-challenged asthmatic animals, significantly slowed the production of inflammatory cells and mediators as well as relaxed the bronchial tubes, suggesting that S-petasin has both anti-inflammatory and bronchodilator properties (Shih 2009). An animal model testing butterbur extract observed similar anti-inflammatory effects on asthmatic mice (Brattström 2010).

Boswellia serrata

Evidence suggests that compounds within the gum resin of boswellia (Boswellia serrata, also known as frankincense) modulate the inflammatory processes that drive asthma symptoms. Boswellia extracts have been shown to inhibit leukotriene synthesis and suppress release of IgE and inflammatory cytokines (Soni 2021; Roy 2019; Ammon 2016). In addition, a study using an animal model of asthma found treatment with boswellia reduced symptoms of asthma and prevented asthma-related diminishment in bacterial diversity in the gut microbiome (Suther 2022).

In a controlled trial, 32 people with asthma were assigned to receive standard medical treatment plus 500 mg per day of boswellia extract, formulated as a phytosome to enhance absorption, or standard medical treatment alone. After four weeks the need for acute inhaler therapy was reduced in the boswellia group but not the standard care group (Ferrara 2015). In another trial, 40 asthmatic subjects were randomized to receive either 300 mg boswellia extract or placebo three times daily for six weeks. While improvement was seen in only 27% of subjects receiving placebo, 70% of those receiving boswellia extract experienced improved performance on tests of lung function and reduction in symptoms such as breathlessness, wheezing, and number of attacks. The boswellia group also exhibited decreased eosinophil count and lower erythrocyte sedimentation rate (ESR)—measures of allergy and inflammation, respectively (Gupta 1998).

Herbal combinations containing boswellia have also shown promise in treating asthma. In a randomized placebo-controlled trial in 36 subjects with mild-to-moderate asthma, 200 mg per day of a one-to-one combination of Boswellia serrata extract (standardized to contain 15% acetyl-11-keto-beta-boswellic acid [AKBA]) plus Aegle marmelos extract (standardized to contain 0.3% imperatorin) reduced asthma symptoms after 14 days compared with placebo. By day 56, levels of IL-4 decreased and levels of interferon-gamma increased in those treated with the herbal combination, indicating an immunological shift away from allergic airway inflammation. In addition, peak expiratory flow rate (a measure of respiratory function) increased by 90.00 L/minute in subjects who received the herbal combination versus 43.85 L/minute in those who received placebo (Yugandhar 2018). Another trial that included 63 people with asthma found a combination of boswellia, curcumin, and licorice root, taken three times daily for four weeks, significantly reduced levels of leukotriene C4 (LTC4) and measures of oxidative stress compared with placebo (Houssen 2010).

Boswellia has also demonstrated antiviral and antibacterial activity, and therefore may be useful for preventing or treating lung infections in people with asthma (Jaroš 2022; Jamshidi 2022; Almutairi 2022).

Aegle marmelos

Aegle marmelos, commonly known as bael, is a plant native to parts of southeast Asia. Aegle marmelos has a long history of use in the traditional Ayurvedic system of herbal medicine for treating a wide array of conditions, including respiratory infections (Manandhar 2018). It is high in nutrients and phytochemicals such as carotenoids, flavonoids, and phenolic compounds with antioxidant, antimicrobial, and anti-inflammatory properties (Sharma 2022; Venthodika 2021). Aegle marmelos extract has demonstrated antihistamine effects to promote relaxant activity in tracheal tissue in the laboratory and reduced respiratory tissue damage and normalized T-helper 1 (Th1) and T-helper 2 (Th2) cytokine imbalance in an animal model of airway inflammation (Yugandhar 2018; Arul 2004). It has also been shown to inhibit inflammation-inducing enzymes (Rajaram 2018).

In a randomized placebo-controlled trial in 36 subjects with mild-to-moderate asthma, 200 mg per day of a one-to-one combination of Aegle marmelos extract (standardized to contain 0.3% imperatorin) plus Boswellia serrata extract (standardized to contain 15% AKBA) reduced asthma symptoms after 14 days compared with placebo. By day 56, levels of IL-4 decreased and levels of interferon-gamma increased in those treated with the herbal combination, indicating an immunological shift away from allergic airway inflammation. Furthermore, peak expiratory flow rate (a measure of lung function) increased more than two-fold in those who received the herbal combination versus placebo (+90.00 L/minute vs. +43.85 L/minute, respectively) (Yugandhar 2018).

Andrographolide

Andrographolide is a compound extracted from andrographis (Andrographis paniculata), an Asian plant used traditionally to treat respiratory infections (Jayakumar 2013). In preclinical studies of asthma, andrographolide has been found to suppress T-cell activity involved in asthma, scavenge free radicals, modulate inflammatory signaling pathways, reduce inflammatory cytokine release, decrease immune cell infiltration into lung tissue, and improve mild-to-severe asthma (Yu 2021; Peng 2016; Li 2009; Chakraborty 2019). Other preclinical research suggests andrographolide has a relaxing effect on the smooth muscles of the trachea, and may therefore help reduce airway constriction (Ozolua 2011).

Saffron

Saffron (stigma of Crocus sativus) is a culinary and medicinal herb known for its bright red-orange color. The carotenoid pigments responsible for saffron’s color, crocin and crocetin, also possess biological activities including anti-inflammatory, oxidative stress-reducing, anti-degenerative, antidepressant, and others (Cerdá-Bernad 2022). Preclinical research indicates crocin extracted from saffron can modulate inflammatory signaling and reduce allergy-like hyper-reactivity of the immune system (Abdi 2022). In an animal model of asthma, safranal (another saffron constituent) reduced IgE levels, inhibited mast cell activation, and balanced T-cell cytokines to alleviate asthma; it also suppressed molecules involved in the anaphylactic reaction such as histamine and LTC4 (Lertnimitphun 2021). Saffron may further reduce airway constriction through relaxant activity on smooth muscles in the airways (Mokhtari-Zaer 2015).

In a randomized placebo-controlled trial that included 80 people with mild-to-moderate asthma, 100 mg saffron daily for eight weeks improved performance on lung function tests and lowered levels of anti-heat shock protein antibody 70 (anti-HSP70), which are elevated in asthma, as well as high-sensitivity C-reactive protein (hsCRP), a marker of inflammation (Hosseini 2018). Another report from the same trial indicated saffron reduced asthma symptoms and frequency of inhaler use. In addition, saffron decreased blood pressure, triglyceride and LDL-cholesterol levels, and numbers of eosinophils and basophils (Zilaee 2019).

Tylophora indica (Tylophora asthmatica)

Tylophora indica (T. indica) is a vine whose leaves have been studied as a potential therapy for asthma symptoms. In studies published in the late 60’s and early 70’s, T. indica relieved asthma symptoms more effectively than a control (Shivpuri 1969; Shivpuri 1972; Mathew 1974). Unfortunately, no newer studies have rigorously evaluated T. indica as an asthma treatment. However, investigators recently pooled the data from the older trials and found that the treatment effect remained significant after adjustment for variables (Clark 2010). They concluded that “…Tylophora indica showed potential to improve lung function…”.