BACKGROUND: In recent studies, afatinib, a second-generation inhibitor, showed superior outcomes, when compared to the first-generation of EGFR-tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, in patients with advanced non-small cell lung cancer (NSCLC) harboring mutations of epidermal growth factor receptor (EGFR). Patients who receive TKIs with a significant initial efficacy, inevitably experience an acquired resistance (AR) within 9 to 13 months. Traditional Korean medicine may have synergistic effects when combined with chemotherapy or radiotherapy. The purpose of this trial is to assess whether afatinib plus HAD-B1 improves disease control rates (DCRs) compared with afatinib alone and to evaluate the efficacy and safety of HAD-B1 for finding the proper dose.

METHODS: This is a randomized, double-blind, placebo-controlled, multi-center, therapeutic, exploratory clinical trial. This trial is designed to determine whether HAD-B1 combined with afatinib results in better DCRs with less toxicity than afatinib alone. A total of 66 NSCLC patients with EGFR mutations will be randomly assigned to treatment group 1 (afatinib 40 mg/day plus HAD-B1 972 mg), treatment group 2 (afatinib 40 mg/day plus HAD-B1 1944 mg) and a control group (afatinib 40 mg/day). Afatinib combined with HAD-B1 or with a placebo will be administered to the participants for 12 weeks. The primary endpoint is a comparison of the DCRs among groups. Secondary endpoints are comparisons of the complete response (CR) and the partial response (PR) to the treatment, the stability of the disease (SD), progression free survival (PFS), time to progression (TTP), and tumor marker (CEA, NSE) and WBC differential count (LMR, NLR) and natural killer cell activity and quality of life (QOL) among groups.

DISCUSSION: The results from this clinical trial will provide evidence of efficacy and safety of HAD-B1 in EGFR positive and locally advanced or metastatic NSCLC patients who need afatinib therapy.

LI13109F is a novel herbal composition containing the extracts of Boswellia serrata gum resin and Aegle marmelos fruit. This composition dampens leukotriene dependent inflammatory reactions via inhibiting 5-lipoxygenase pathway. In a Sephadex LH-20 induced airway inflammation model of Sprague Dawley rats, LI13109F significantly reduced infiltrated granulocyte population in the bronco-alveolar lavage fluid and normalized Th1/Th2 cytokine balance. Further, a 56-day placebo-controlled and randomized double blind study (Clinical Trial Registration No. CTRI/2016/10/007393) on subjects with mild to moderate asthma has evaluated the clinical efficacy of LI13109F. The study subjects received either 200 mg/day of LI13109F (n = 18) or a similar dosage of placebo (n = 18). At the end of the trial period, LI13109F conferred significant improvements in the clinical parameters; the emotional function (p = .0305) and asthma symptoms scores (p = .0002) were improved even at 14 days, compared with the placebo. Further, 56 days supplementation of LI13109F resulted in significant increase in serum IFN-γ (p = .0014) and reduction in IL-4 (p = .0497), compared with placebo. LI13109F supplementation did not yield any serious adverse events or any abnormal observations in routine laboratory examinations during the study. Together, these observations suggest that LI13109F (AlvioLife®) is tolerable and an effective intervention for management of mild to moderate asthma such as airway inflammation.

OBJECTIVE: To search major Traditional Persian Medicine (TPM) textbooks for medicinal plants used to treat asthma. The conformity of the TPM findings on the anti-asthmatic efficacy of plants with the findings of pharmacological studies was also explored.

METHODS: Major TPM textbooks were hand searched to find medicinal plants used for the treatment of asthma. Scientific names of TPM-suggested plants were determined using botanical databases and were used for a multidatabase electronic search in PubMed, Scopus, ScienceDirect and Google Scholar databases. Then, the antiasthmatic effectiveness of TPM-recommended plants was verified in view of the findings from modern pharmacological investigations.

RESULTS: According to the main TPM texts, Adianthum capillus-veneris, Boswellia oleogumresin, Crocus sativus, Glycyrrhiza glabra, Hyssopus officinalis and Ruta graveolens were the most efficacious medicinal plants for the treatment of asthma. This finding was confirmed by pharmacological studies which showed counterbalancing effects of the above-mentioned plants on inflammation, oxidative stress, allergic response, tracheal smooth muscle cell constriction and airway remodeling.

CONCLUSION: The strong ethnobotanical background of plants used in TPM could be a valuable tool to find new anti-asthmatic medications. In this review, TPM-suggested anti-asthmatic plants were found to possess several mechanisms relevant to the treatment of respiratory diseases according to the information retrieved from modern pharmacological studies. This high degree of conformity suggested further proof-of-concept trials to ascertain the role of these plants in the routine management of asthmatic patients.

OBJECTIVE: The combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) is recommended for the treatment of patients with mild-to-severe persistent asthma. However, given the lack of definite and safe therapies, complementary or alternative medicines are frequently used by asthmatic patients in combination with standard treatments.

PATIENTS AND METHODS: A group of asthmatic subjects have been enrolled in this multicenter study; after having verified the compliance to their current medical therapy (ICS + LABAs), the subjects have been randomized to receive Casperome® 500 mg/day or no additional treatment for a period of 4 weeks. They were also asked to keep track of the number of inhalations required per day and any adverse events through a daily form.

RESULTS: A total of 32 subjects were enrolled in the study. Subjects receiving Casperome® 500 mg/day in addition to the standard ICS + LABAs treatment showed a decrease in the number of inhalations needed compared to patients who did not receive Casperome® therapy. The treatment was well tolerated and only mild-moderate adverse events were registered.

CONCLUSIONS: The use of Casperome® 500 mg/day is beneficial for asthmatic patients as it helps reduce the need for inhalation therapy with ICS + LABA.

A 61-year-old man complained of cough and dyspnoea after exposure to colophony-containing solder fumes at work. A histamine challenge test confirmed airway hyper-responsiveness, and colophony-challenge demonstrated a 16.7% drop in peak expiratory flow rate (PEFR), supporting a diagnosis of colophony-induced occupational asthma. At review, the patient presented with cough, dyspnoea and wheeze that occurred acutely when exposed to the fumes from burning incense during Easter Saturday services, necessitating his departure from the church. Inhalation challenge tests using two blends of incense used at his church (Greek and Vatican) led to identical symptoms and a significant reduction in forced expiratory volume in 1 s 15 min after exposure and PEFRs up to 48 h after exposure, indicating an early and late phase asthmatic reaction. This is the first report of coexistent colophony and incense-induced asthma. The similarities in chemical structures between abietic acid in colophony and boswellic acid in incense suggest a common mechanism.

OBJECTIVE: To assess the efficacy of a combination of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa) as natural leukotriene inhibitor, antiinflammatory and antioxidant products respectively in controlling bronchial asthma.

SUBJECTS AND METHODS: The study comprised 63 patients with bronchial asthma that are further subdivided into two groups .Group 1 receiving oral capsule (combined herb) in a soft-gelatin capsule 3 times daily for 4weeks and group 2 receiving placebo. Plasma leukotriene C(4) (LTC(4))(,) nitric oxide (NO) and malondialdehyde (MDA) levels were measured and pulmonary function was also assessed in all patients enrolled in the study.

RESULTS: There was a statistically significant decrease in the plasma levels of LTC(4), (MDA), and NO in target therapy group when compared with placebo group.

CONCLUSION: The used extract contained Boswellia serrata, Curcuma longa and Glycyrrhiza has a pronounced effect in the management of bronchial asthma.

Patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions, and fruits and vegetables (at least five servings a day). Physicians may need to be more cautious when prescribing antibiotics to children in their first year of life when they are born to families with a history of atopy. More research is needed to establish whether supplementation with probiotics (lactobacillus and bifidobacterium) during the first year of life or after antibiotic use decreases the risk of developing asthma and allergic rhinitis. Despite a theoretic basis for the use of vitamin C supplements in asthmatic patients, the evidence is still equivocal, and long-term studies are needed. The evidence is stronger for exercise-induced asthma, in which the use of vitamin C supplementation at a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma. Long-term studies of fish oil and vitamin C are needed for more definite answers. For the patient interested in incorporating nutritional approaches, vitamin C and fish oils have a safe profile. However, aspirin-sensitive individuals should avoid fish oils, and red blood cell magnesium levels may help in making the decision whether to use additional magnesium supplements. Combination herbal formulas should be used in the treatment of asthma with medical supervision and in collaboration with an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia and gingko, may be used singly as adjuncts to a comprehensive plan of care if the patient and practitioner have an interest in trying them while staying alert for drug-herb interactions. No data on the long-term use of these single herbs in asthma exist. For the motivated patient, mind-body interventions such as yoga, hypnosis, and biofeedback-assisted relaxation and breathing exercises are beneficial for stress reduction in general and may be helpful in further controlling asthma. Encouraging parents to learn how to massage their asthmatic children may appeal to some parents and provide benefits for parents and children alike. Acupuncture and chiropractic treatment cannot be recommended at this time, although some patients may derive benefit because of the placebo effect. For patients with allergic rhinitis, there are no good clinical research data on the use of quercetin and vitamin C. Similarly, freeze-dried stinging nettle leaves may be tried, but the applicable research evidence also is poor. Further studies are needed to assess the efficacy of these supplements and herbs. Homeopathic remedies based on extreme dilutions of the allergen may be beneficial in allergic rhinitis but require collaboration with an experienced homeopath. There are no research data on constitutional homeopathic approaches to asthma and allergic rhinitis. Patients with COPD are helped by exercise, pulmonary rehabilitation, and increased caloric protein and fat intake. Vitamin C and n-3 supplements are safe and reasonable; however, studies are needed to establish their efficacy in COPD. On the other hand, there are convincing data in favor of N-acetyl-cysteine supplementation for the patient with COPD at doses ranging between 400 and 1200 mg daily. Red blood cell magnesium levels may guide the use of magnesium replacement. The use of L-carnitine and coenzyme Q10 in patients with COPD needs further study. The addition of essential oils to the dietary regimen of patients with chronic bronchitis is worth exploring. Patients with upper respiratory tract infections can expect a shorter duration of symptoms by taking high doses of vitamin C (2 g) with zinc supplements, preferably the nasal zinc gel, at the onset of their symptoms. Adding an herb such as echinacea or Andrographis shortens the duration of the common cold. The one study on Elderberry's use for the flu was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting, but more studies should be performed. Saline washes may be helpful to patients with allergic rhinitis and chronic sinusitis. Patients also may try the German combination (available in the United States) of elderberry, vervain, gentian, primrose, and sorrel that has been tested in randomized clinical trials. Bromelain is safe to try; the trials of bromelain supplementation were promising but were never repeated. The preceding suggestions need to be grounded in a program based on optimal medical management. Patients need to be well educated in the proper medical management of their disease and skilled at monitoring disease stability and progress. Asthmatic patients need to monitor their bronchodilator usage and peak flow meter measurements to step up their medical treatment in a timely manner, if needed. Patients welcome physician guidance when exploring the breadth of treatments available today. A true patient-physician partnership is always empowering to patients who are serious about regaining their function and health.

The gum resin of Boswellia serrata, known in Indian Ayurvedic system of medicine as Salai guggal, contains boswellic acids, which have been shown to inhibit leukotriene biosynthesis. In a double-blind, placebo-controlled study forty patients, 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness, bronchial asthma, of 9.58 +/- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks. 70% of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea, rhonchi, number of attacks, increase in FEV subset1, FVC and PEFR as well as decrease in eosinophilic count and ESR. In the control group of 40 patients 16 males and 24 females in the age range of 14-58 years with mean of 32.95 +/- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks. Only 27% of patients in the control group showed improvement. The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma.