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Bronchial asthma as neurogenic paroxysmal inflammatory disease: A randomized trial with carbamazepine

Open ArchivePublished:April 06, 2006DOI:https://doi.org/10.1016/j.rmed.2006.02.018

      Summary

      Purpose

      Based on the assumption that bronchial asthma has not only inflammatory, but also certain neurogenic paroxysmal mechanism and pathophysiological links with other non-epileptic paroxysmal inflammatory diseases—migraine and trigeminal neuralgia, we decided to investigate efficacy of antiepileptic drug carbamazepine in patients with moderate persistent or severe asthma.

      Methods

      Sixty-three patients completed randomized double-blind, placebo-controlled trial.

      Results

      Stable remission was achieved after carbamazepine treatment in 25 patients in active group (n=33). No significant improvement was registered in patients of placebo group (n=30). Following open-label treatment shows high and stable antiasthmatic efficacy of carbamazepine monotherapy.

      Conclusions

      Carbamazepine showed high efficacy in therapy of moderate persistent or severe bronchial asthma. Antiasthmatic activity of carbamazepine can be considered as influence on neurogenic mechanisms of asthma. We suppose that it is possible to use carbamasepine for therapy of bronchial asthma in clinical practice.

      Keywords

      Introduction

      Bronchial asthma still stays a heavy controlled disorder: burden of asthma worldwide includes thousands of lives and billions of US dollars annually.

      Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institutes of Health, NHLBI/WHO workshop report, update 2004.

      The drug treatment of asthma has remained essentially unchanged over the past three decades in terms of the use of corticosteroids, β2 agonist and theophylline.
      • Masoli M.
      • Fabian D.
      • Holt S.
      • Beasley R.
      GINA Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report.
      In spite of definite achievements, like use of leukotriene antagonists, pharmacotherapy of asthma remains a serious problem. Moreover, some drugs for asthma therapy can be dangerous for patients.
      Asthma mortality: summary of a round-table discussion, New York, January 1997.
      As we know, bronchial asthma is an inflammatory disease,

      Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institutes of Health, NHLBI/WHO workshop report, update 2004.

      and neurogenic inflammation may play important role in asthma mechanisms.
      • Joos G.F.
      • De Swert K.O.
      • Schelfhout V.
      • Pauwels R.A.
      The Role of Neural Inflammation in Asthma and Chronic Obstructive Pulmonary Disease.
      But we must remember that asthma is inflammatory disease with paroxysmal clinical picture.

      Canadian asthma consensus report. CMAJ 199;161(11Suppl):S1–5.

      We also know, that migraine and trigeminal neuralgia also are inflammatory diseases with paroxysmal clinical picture,

      Kryzhanovskii GN. Determinant structures in pathologic conditions of the nervous system. Generator mechanisms of neuropathologic syndromes. Meditsina, Moscow, 1980.

      and neurogenic inflammation plays important role in mechanisms of these diseases.
      • Hardebo J.E.
      A cortical excitatory wave may cause both the aura and the headache of migraine.
      • Strittmatter M.
      • Grauer M.
      • Isenberg E.
      • Hamann G.
      • Fischer C.
      • Hoffmann K.H.
      • et al.
      Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with trigeminal neuralgia.
      Some antiepileptic drugs are very effective in therapy of migraine
      • Hering R.
      • Kuritzky A.
      Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo.
      • Corbo J.
      The role of anticonvulsants in preventive migraine therapy.
      and trigeminal neuralgia
      • Dalessio D.J.
      The major neuralgias, postinfection neuritis, and atypical facial pain.
      • Spina E.
      • Perugi G.
      Antiepileptic drugs: indications other than epilepsy (review).
      —in more than 80% of cases. But if antiepileptic drugs are so effective in therapy of neurogenic inflammatory paroxysmal diseases, is it possible that some antiepileptic drugs are also effective in asthma therapy?
      Our previous results confirm our hypothesis: carbamazepine and valproates are highly effective in asthma monotherapy.
      • Lomia M.
      • Pruidze M.
      • Chapichadze Z.
      Bronchial asthma as neurogenic paroxysmal disease—high effectiveness of carbamazepine in asthma monotherapy.
      • Lomia M.
      • Chapichadze Z.
      • Pruidze M.
      • Platonov P.
      Efficacy of monotherapy with carbamazepine and valproic acid in patients with bronchial asthma: is asthma a neurological disease?.
      Data of other authors also are quite remarkable: treatment of children with epilepsy and concomitant asthma by antiepileptic drugs significantly reduces not only severity of epilepsy, but also reduces the severity of asthma.

      Ivanova NA. Epilepsy in structure of concomitant diseases in children with bronchial asthma and principles of complex therapy [Russian]. In: Modern principles of treatment of children with relapsing and chronic bronchial and lungs diseases. Leningrad; 1987. p. 89–91.

      Due to this we decided to perform double-blind randomized placebo-controlled trial of antiepileptic drug carbamazepine in patients with moderate persistent or severe bronchial asthma. The objective of this study was to assess, in a randomized double-blind placebo-controlled manner, efficacy of 3-months-long peroral administration of carbamazepine on pulmonary function assessed by PEF, forced expiratory volume in 1s (FEV1), severity of daytime asthma scores and number of night awakening per week due to asthma symptoms in patients with moderate-to-severe persistent and poorly managed bronchial asthma.
      We decided to perform trial in relatively small number of patients, because we anticipated antiasthmatic efficacy of antiepileptic agents similar to high efficacy of anticonvulsants in migraine and trigeminal neuralgia.

      Methods

      Patients

      Aim of study was to evaluate efficacy of carbamazepine in treatment of bronchial asthma. Patients aged 16–65 years old with moderate-to-severe persistent asthma were recruited for study participating. Study was performed in Chinese Medical Centre, Tbilisi, Georgia. Patients were diagnosed according to the American Thoracic Society definition of asthma
      American Thoracic Society
      Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma.
      and according to GINA recommendations.

      Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institutes of Health, NHLBI/WHO workshop report, update 2004.

      Severity of asthma was classified according GINA.

      Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institutes of Health, NHLBI/WHO workshop report, update 2004.

      The investigators selected adult patients who had poorly controlled asthma despite maintenance therapy with inhaled or oral corticosteroids, beta-agonists, cromoglycates, antihistamines or theophylline.
      Inclusion criteria: out-patients, history of disease at least for 1 year, poorly controlled asthma due to various reasons, absence of long-term remissions of asthma (lasting more than 1 month), and if pulmonary function testing demonstrated at least 12% acute response in FEV1 to beta-agonist inhalation.
      Patients were excluded if they had long-lasting remissions of asthma (more than 1 month) or if their asthma was strictly seasonal, if they had concomitant severe diseases, if they suffered from any serious illness that could make their participation in the study hazardous or could obscure the evaluation of the effect of the study drug, if they had an allergy or intolerance to carbamazepine or its derivatives, age younger than 16 years old, and long-term history of smoking. Women who were breast-feeding, pregnant or not practicing a reliable method of birth control were excluded.

      Study design

      The study was a single-centre, double-blind, randomized, placebo-controlled trial. Before the blind phase of study, patients were enrolled into a 4-week run-in period during which they completed daily diary cards, attended laboratory sessions for pulmonary function testing, and were observed during office visits for documentation of symptoms. Patients also were instructed in the administration of blind capsules (with active drug or placebo) and of using Mini-Wright peak flow meters. The 74 patients who remained eligible after the run-in period were randomly assigned to a 13-week (3 months), double-blind phase of treatment with either 100mg capsules of carbamazepine (N=37) or placebo (N=37). Randomization was computer-generated in blocks of two treatment regimens: active drug and placebo. Patients received capsules equal in size, color, weight and taste, and placed in standard packets. Allocation sequence and computerized assignation of patients to their groups was established by invited programmer. Participants were enrolled by investigators. Patients agreed to continue their treatment with corticosteroids, oral theophyllines, beta-agonists, cromoglycates and antihistamines.
      During the 13-week study period, active drug and placebo were supplied in identical packets, sufficient for 4 weeks of administration. Patients returned used packets at each clinic visit and amount of capsules in these packets were subsequently accounted as an independent evaluation of compliance. Once in 4 weeks patients received the new packet from allocated packets.
      For minimization of adverse reactions dosage of carbamazepine and placebo were increased gradually: first 5 days patients received 1 capsule one time per day, next 5 days—1 capsule twice per day, next 5 days—2 capsule twice per day, and then—2 capsules three times per day till to end of study. This practice is very usual for administration of antiepileptic drugs. In case of appearing transitory adverse reactions during dose growth patients were allowed to return to previous smaller dose for 5 days and then begin dose titration in the same mode.
      Morning and evening PEF were registered by patients (Mini-Wright peak flow-meters, Wright-McKerrow scale) before the study, every day throughout the study and after the study. FEV1 and additionally PEF were registered by portable spirometer “Spirodoc” (MIR, Italy) before the study, every week during morning clinical visits and after the study.
      FEV1 before and after use of 400μg (4 puffs) inhaled salbutamol—was registered in the morning before and after the study.
      Routine blood and urine analysis was evaluated in each patient before the study, once a month during clinical visits and after the study.
      Every day throughout the study in their diary cards patients recorded the severity of daytime asthma, using a 0–3 scale with 0 indicating no symptoms and 3 indicating severe symptoms, nighttime awakenings due to asthma symptoms, adverse events, their morning and evening peak-flow data and usage of their routine antiasthmatic drugs except carbamazepine. At each clinic visit during the trial diary-symptom cards were collected, maximum expiratory flow-volume curves were obtained and patients were interviewed as to incidence and severity of daytime and nocturnal symptoms.
      In special circumstances, when patients could not visit the site due to various reasons, we planned missed clinical visit to nearest possible day or investigator physicians visited to patients’ home if it was requested by patient.
      Patients were allowed to abandon any other previously prescribed routine antiasthmatic treatment under our physicians’ careful supervision in case of asthma symptoms disappearance, lasted at least 1 month after beginning the trial. The reason of this was our previous clinical experience: after receiving of high positive effect of antiepileptic drugs in asthma our out-patients usually discontinued any other antiasthmatic treatment too abruptly. Due to economical reasons (no effective medical insurance) patients tried to avoid buying non-effective drugs for concomitant use with antiepileptic drug. We strongly advised to reduce long-term peroral or parenteral hormonal therapy gradually, and we gave to patients oral and written instructions concerning danger of systemic adverse effects in case of sudden abandoning of high-dose peroral or parenteral hormonal therapy.
      Our study was compliant with Helsinki Declaration and GCP principles, and study was approved by local Ethics Committee and subjects gave their written consent to participate.
      Endpoint definition: Efficacy of carbamazepine was evaluated by disappearance of any asthmatic syndrome, and normalization of PEF, FEV1 (primary outcomes), daytime scores of asthma, number of nighttime awakening per week due to asthma symptoms and also by discontinuation of any other antiasthmatic therapy except carbamazepine (secondary outcomes).
      Safety of the treatment: the safety of the treatment was evaluated at each visit when patients were questioned for any adverse events and health problems that may have occurred. All unusual signs and symptoms were recorded for further consideration. Routine blood and urine analyses were performed every month throughout the study.
      Adverse events: patients recorded any adverse events on the diary cards and were additionally questioned in a general manner at each visit regarding possible adverse events. Any adverse events reported were graded as mild, moderate, or severe and assessed for any relationship to the study medication.
      Stopping rules of the study were multiple resistant adverse effects of the therapy, abnormalities in laboratory analyses and significant deterioration of asthma symptoms. Patients were allowed to stop participating in out trial in any time.

      Statistical analysis

      The null hypothesis for patients enrolled in trial was that carbamazepine was no better than placebo in improving symptoms of asthma when added to an existing treatment regimen. Wilcoxon signed rank test was used throughout for statistical analysis of non-parametric related data. Mann–Whithey U-test was used for analysis of non-parametric independent data. A P-value ⩽0.05 was considered significant. For statistical analysis of data we used SPSS for Windows (release 11.0). Data are presented as mean±standard deviation.

      Results

      Patients population

      Recruitment was performed from October 4, 2004, to December 24, 2004, and trial lasted till to March 31, 2005. Seventy-four patients were enrolled into the blind phase of the study. Eleven patients were excluded from investigation at the beginning of the trial (4 from carbamazepine group: 3 due to stable side effects—dizziness and somnolence, 1—due to non-compliance, and 7 from placebo group due to non-compliance). Thus, in total 63 patients (33 of carbamazepine group and 30 of placebo group) completed the trial and were analyzed (see Table 1).
      Table 1Baseline characteristics of 63 study patients.
      Groups/variablesCarbamazepine group (n=33)Placebo group (n=30)Significance of difference
      Age (years)50.3±10.845.5±15.8NS (P>0.05)
      Gender
       Male13 (39.4%)12 (40%)NS (P>0.05)
       Female20 (60.6%)18 (60%)NS (P>0.05)
      Duration of asthma (years)12.2±9.416.4±10.7NS (P>0.05)
      Severity of asthma
       Moderate persistent7 (21.2%)8 (26.7%)NS (P>0.05)
       Severe26 (78.8%)22 (73.3%)NS (P>0.05)
      PEF (L/min)234±67242±84NS (P>0.05)
      FEV1 (L)1.13±0.441.20±0.55NS (P>0.05)
      Concomitant medication33 (100%)30 (100%)NS (P>0.05)
      1. Theophylline25 (75.8%)21 (70%)NS (P>0.05)
      2. Beta-agonists22 (66.7%)16 (53.3%)NS (P>0.05)
      3. Steroids17 (51.5%)21 (70%)NS (P>0.05)
      4. Cromoglycates10 (30.3%)10 (33.3%)NS (P>0.05)
      5. Antihistamines7 (21.2%)11( 36.7%)NS (P>0.05)

      Peak expiratory flow

      Analysis of symptoms showed, that asthmatic attacks disappeared after 6–16 days of treatment in 25 patients of carbamazepine group, and also we observed quite gradual increase in peak-flow rates during first month of study.
      After 1 month of the treatment in 25 patients of carbamazepine group we have registered significant increase of peak-flow rates, which gradually persisted during next weeks and almost reached calculated normal level at the end of 3rd month. In other 8 patients of carbamazepine group peak-flow rates remained at the pre-treatment level (see Fig. 1, and Table 2).
      Figure thumbnail gr1
      Figure 1Morning peak-flow rates.
      Table 2Patient characteristics before and after the treatment: carbamazepine and placebo group.
      Groups/variablesCarbamazepine groupPlacebo group
      Before the trialAfter the trialBefore the trialAfter the trial
      # of patients33 (100%)33 (100%)30 (100%)30 (100%)
      # of patients with everyday attacks23 (69.7%)4 (12.1%)**21 (70%)22 (73.3%)
      # of patients without asthma attacks025 (75.8%)**00
      PEF (L/min)234±67388±118**242±84242±84
      % predicted PEF50.9±13.582.3±16.8**51.4±12.551.4±12.0
      FEV1 (L)1.13±0.442.23±0.85**1.20±0.551.23±0.58
      % predicted FEV139.5±13.476.2±20.9**39.8±12.940.9±14.0
      FEV1 increase in % from baseline after salbutamol inhalation16.6±3.48.5±4.7**17.5±4.313.3±5.1
      Daytime scores of asthma (0–3 scale)1.73±1.100.30±0.85**1.67±1.211.63±1.13
      Number of nights per week with awakening due to asthma5.39±2.501.09±2.34**5.13±2.265.07±2.43
      Concomitant medication:33 (100%)7 (21.2%)**30 (100%)30 (100%)
      1. Theophylline25 (75.8%)5 (15.2%)**21 (70%)21 (70%)
      2. Beta-agonists22 (66.7%)7 (21.2%)**16 (53.3%)16 (53.3%)
      3. Steroids17 (51.5%)5 (15.2%)**21 (70%)19 (63.7%)
      4. Cromoglycates10 (30.3%)1 (3.0%)**10 (33.3%)11 (36.7%)
      5. Antihistamines7 (21.2%)3 (9.1)**11( 36.7%)11 (36.7%)
      *Difference between this group and placebo is statistically significant (P0.05).
      **Difference between this group and placebo is statistically significant (P0.01).
      We did not observe any significant changes of peak-flow rates in 30 patients of placebo group.

      Forced expiratory volume in 1s (FEV1)

      FEV1 also increased gradually after the beginning of the trial (see Fig. 2). After 4 weeks of treatment FEV1 in patients of carbamazepine group was significantly higher compared to FEV1 in patients of placebo group. Increase of FEV1 in carbamazepine group has continued till the end of the study. In placebo group FEV1 stayed at pre-treated level (see Fig. 2 and Table 2).
      Figure thumbnail gr2
      Figure 2Morning FEV1, in % from normal FEV1.

      FEV1 before and after inhaled beta-agonist

      Mean increase of morning FEV1 after the use of 400μg (4 puffs) inhaled salbutamol more than by 12% was registered in the morning before the study in patients of active and placebo groups. After the study only patients of placebo group had the mean increase of morning FEV1 after inhaled salbutamol more than by 12%. In patients from carbamazepine group mean increase of morning FEV1 after inhaled salbutamol was only till 8.5±4.7% vs. FEV1 initial level, and this is significantly less in comparison to placebo group (see Table 2).

      Patients without asthmatic attacks

      In 25 patients from 33 (75.8% of carbamazepine group, see Supplementary Table) asthmatic attacks disappeared after 7–15 days of treatment by carbamazepine. Other 8 patients from carbamazepine group and 30 patients from placebo group had asthma attacks till the end of the study (see Table 2). So, we observed appearance and significant growth of the number of patients without asthmatic attacks: at the end of the treatment 25 patients out of 33 patients from carbamazepine group had no asthmatic attacks at all.

      Daytime scores of asthma and number of night awakening per week due to asthma symptoms

      Daytime scores of asthma and night awakening rating due to nocturnal asthma symptoms were decreased significantly after first 4 weeks of study in patients from carbamazepine group, and then stayed on this level till the end of the study. No significant decrease of these parameters occurred in patients from placebo group (see Figure 3, Figure 4, Table 2).
      Figure thumbnail gr3
      Figure 3Daytime scores of asthma (0–3 scale).
      Figure thumbnail gr4
      Figure 4Nights with awakening per week due to asthma.

      Concomitant treatment with routine antiasthmatic drugs

      Twenty-five patients, where treatment by carbamazepine was effective, after 2–4 weeks of study treatment discontinued any previously prescribed treatment (see Table 2). No one from these patients received high doses of peroral hormones during years, and due to this they were allowed to abandon their antiasthmatic therapy except carbamazepine in case of excellent efficacy of investigational drug, as they were instructed in run-in period before the clinical phase of study.

      Adverse events

      In 74 patients enrolled into the study 3 patients of active group (1 man and 2 women) were excluded from the study due to stable moderate adverse events—dizziness and somnolence. In 7 patients (2 men and 5 women) we observed transient and mild adverse events only in first 2 weeks after the beginning of the study, and they did not excluded from the study. In active group dizziness had 2 women and 1 man, headache—1 man and 2 woman. In placebo group somnolence had 1 woman.

      Following open-label treatment

      After randomized double-blind phase of the study patients continue treatment in open-label mode. According to our data, 6 months after the start of our treatment by carbamazepine all 25 responders of carbamazepine group continued treatment by this drug after the study. Peak-flow rates in all these patients remained in the normal range after finishing the blind phase of trial. All 25 responders did not take any antiasthmatic treatment except carbamazepine and they did not have any signs of asthma.

      Discussion

      In this study it become possible to prove that in more than 75.8% of patients from carbamazepine group asthma attacks were avoided by the use of carbamazepine. In carbamazepine group in compare to placebo group the daytime scores of asthma and number of nights with awakening per week due to asthma decreases significantly, in 25 patients asthmatic attacks disappeared completely, PEF and FEV1 increases significantly, stable remission was achieved after treatment during months, concomitant antiasthmatic therapy is reduced and even discontinued.
      Such results confirm the results of our previous trials.
      • Lomia M.
      • Pruidze M.
      • Chapichadze Z.
      Bronchial asthma as neurogenic paroxysmal disease—high effectiveness of carbamazepine in asthma monotherapy.
      • Lomia M.
      • Chapichadze Z.
      • Pruidze M.
      • Platonov P.
      Efficacy of monotherapy with carbamazepine and valproic acid in patients with bronchial asthma: is asthma a neurological disease?.
      • Lomia M.
      • Pruidze M.
      • Chapichadze Z.
      Bronchial asthma as neurogenic paroxysmal inflammatory disease—high effectiveness of antiepileptic drug oxcarbazepine in asthma monotherapy.
      Some previous experimental findings also confirm our results: it was shown that carbamazepine suppresses bronchoconstriction in guinea pigs, induced by some neuromediators and biologically active agents, including substance P.
      • Bianchi M.
      • Rossoni G.
      • Maggi R.
      • Panerai A.E.
      • Berti F.
      Effects of carbamazepine on plasma extravasation and bronchoconstriction induced by substance P, capsaicin, acetaldehyde and histamine in guinea-pig lower airways.
      Other confirmation of our results is that the treatment of children with epilepsy and concomitant asthma by antiepileptic drugs also significantly reduces the severity of asthma.

      Ivanova NA. Epilepsy in structure of concomitant diseases in children with bronchial asthma and principles of complex therapy [Russian]. In: Modern principles of treatment of children with relapsing and chronic bronchial and lungs diseases. Leningrad; 1987. p. 89–91.

      It seems quite possible that bronchial asthma is mainly paroxysmal neurogenic inflammatory disorder and airways inflammation in asthma is not only immune, but also neurogenic process. Role of nervous system is widely recognized in regulation of bronchial tone,

      Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institutes of Health, NHLBI/WHO workshop report, update 2004.

      but no one tried to suppress inflammation and paroxysmal nature of bronchoconstriction in asthma by antiepileptic drugs, like in therapy of neurogenic paroxysmal inflammatory disorders migraine
      • Dalessio D.J.
      The major neuralgias, postinfection neuritis, and atypical facial pain.
      • Spina E.
      • Perugi G.
      Antiepileptic drugs: indications other than epilepsy (review).
      and trigeminal neuralgia.
      • Hardebo J.E.
      A cortical excitatory wave may cause both the aura and the headache of migraine.
      • Corbo J.
      The role of anticonvulsants in preventive migraine therapy.
      It is also possible that carbamazepine and some other anticonvulsants have antiasthmatic activity due their direct peripheral influence on airways wall. But combination of strong antimigrenous and antiasthmatic activity of antiepileptic drugs does not confirm this assumption. It is known that almost all other drugs with peripheral activity in migraine can provoke asthma attacks and vice versa: so, non-steroidal anti-inflammatory drugs are effective for the treatment of migraine,
      • Lipton R.B.
      • Goldstein J.
      • Baggish J.S.
      • Yataco A.R.
      • Sorrentino J.V.
      • Quiring J.N.
      Aspirin is efficacious for the treatment of acute migraine.
      but at the same time they are contraindicated in bronchial asthma
      • Covar R.A.
      • Macomber B.A.
      • Szefler S.J.
      Medications as asthma triggers.
      ; beta-adrenergic agonists are effective for bronchial asthma,

      Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institutes of Health, NHLBI/WHO workshop report, update 2004.

      but beta-adrenoblockers—for migraine,
      • Snow V.
      • Weiss K.
      • Wall E.M.
      • Mottur-Pilson C.
      Pharmacologic management of acute attacks of migraine and prevention of migraine headache.
      and at the same time beta-adrenoblockers are contraindicated in bronchial asthma.
      • Covar R.A.
      • Macomber B.A.
      • Szefler S.J.
      Medications as asthma triggers.
      If we suppose peripheral influence of antiepileptic drugs on bronchial tone, we must make assumption about existence of some new types of peripheral receptors in airways wall. We also could not find some evidences about peripheral therapeutic activity of carbamazepine in medical literature.
      It is interesting that carbamazepine shows efficacy also in some other neurogenic inflammatory disorders. Some authors described patients with psoriasis which had dramatic improvement of their condition after administration of carbamazepine.
      • Smith K.J.
      • Skelton H.G.
      Accidental success with carbamazepine for psoriatic erythroderma.
      • Goyal N.N.
      • Dhurat R.S.
      • Jerajani H.R.
      Carbamazepine in Reuter's sindrome.
      Similar to asthma neurogenic inflammation plays important role in mechanism of psoriasis,
      • Raychaudhuri S.P.
      • Raychaudhuri S.K.
      Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis.
      • Joseph T.
      • Kurian J.
      • Warwick D.J.
      • Friedmann P.S.
      Unilateral remission of psoriasis following traumatic nerve palsy.
      and substance P plays important role in inducing of this inflammation.
      • Farber E.M.
      • Nickoloff B.J.
      • Recht B.
      • Fraki J.E.
      Stress, symmetry, and psoriasis: possible role of neuropeptides.
      • Schon M.P.
      • Boehncke W.-H.
      Psoriasis.
      Due to high efficacy of carbamazepine in patients with moderate persistent and severe asthma we suppose that it is possible to use carbamasepine for therapy of bronchial asthma in clinical practice.

      Acknowledgements

      The authors thank Dr. Antonina Nabokova, Dr. Zaza Chapichadze and Dr. Peter Platonov for their valuable assistance.

      Appendix A. Supplementary Materials

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