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JSM Clinical Case Reports

Successful management by Combination of Alternaria alternata Subcutaneous Allergen Immunotherapy with Omalizumab in five cases of Chronic Rhinosinusitis with or without Nasal Polyps Co-morbid Asthma

Case Report | Open Access Volume 9 | Issue 1 |

  • 1. Department of Pulmonology, National Allergy Centre, India
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Corresponding Authors
Department of Pulmonology, National Allergy Centre, New Delhi, India, Tel: 09312285947; Email: pc_kathuria@yahoo.com
Abstract

Allergen Immunotherapy is a unique and effective therapeutic option in patients allergic to molds. Alternaria alternata is known to be a significant source of fungi aeroallergens. Sensitization to A. alternata is a risk factor for development and persistence of Chronic Rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps Co-morbid Asthma. The role of Allergen Immunotherapy (AIT) by Alternaria alternata allergen extract combined with Omalizumab has been evaluated in very few studies. In our five cases, the combined effect of Alternaria alternata Subcutaneous Immunotherapy (SCIT) with Omalizumab was safe, effective, and synergistic, sustained and achieved the maintenance dose faster. Our conclusion was based on significant reduction in symptom and medication scoring by Asthma Control Test (ACT), Rhinitis Control Assessment Test (RCAT), Sino-nasal Outcome Test (SNOT-22), Improvement in Peak Expiratory Flow Rate (PEFR) variability, Immunological (Ratio of Specific IgE to Total IgE for Alternaria alternata), Endoscopic and Radiographic parameters after 1 year of treatment. We suggest a causative role of Alternaria alternata allergen in the pathogenesis of Chronic Rhinosinusitis with or without nasal polyps Co-morbid Asthma.

Keywords

Subcutaneous Immunotherapy (SCIT); Allergen specific Immunotherapy (ASIT); Peak Expiratory Flow Rate (PEFR); Severe Asthma with Fungal sensitization (SAFS); Functional Endoscopic Sinus Surgery (FESS); Acute Exacerbation of respiratory diseases (AERD); Rhinitis Control assessment Test (RCAT); Asthma Control Assessment (ACT); Sino-nasal Outcome Test22 (SNOT-22); Maximum tolerated Dose (MTD).

 

Citation

Kathuria PC, Rai M, Rai D (2021) Successful management by Combination of Alternaria alternata Subcutaneous Allergen Immunotherapy with Omalizumab in five cases of Chronic Rhinosinusitis with or without Nasal Polyps Co-morbid Asthma. JSM Clin Case Rep 9(1): 1182.

ABBREVIATIONS

CRSwNP: Chronic Rhinosinusitis with Nasal Polyp; CRSsNP: chronic Rhinosinusitis without Nasal Polyp; SCIT: Subcutaneous Immunotherapy; ASIT: Allergen specific Immunotherapy; PEFR: Peak Expiratory Flow Rate; SAFS: Severe Asthma with Fungal Sensitization; FESS: Functional Endoscopic Sinus Surgery; AERD: Acute Exacerbation of respiratory diseases; RCAT: Rhinitis Control assessment Test; ACT: Asthma Control Assessment; SNOT: Sino-nasal Outcome Test; MTD: Maximum tolerated Dose.

INTRODUCTION

Chronic Rhinosinusitis is defined as an inflammatory disorder of the mucosa of nasal passages and the paranasal sinuses that lasts for at least 12 weeks with relevant symptomatology or signs with at least 2 of the following:

a) Nasal Obstruction, b) Facial Pain/ Pressure/ Fullness, c) Hyposmia/ Anosmia, d) Mucopurulent drainage and objective evidence of mucous inflammation of at least 1 of the following: a) Polyps in the nasal cavity in middle meatus, b) Edema in the middle meatus or anterior ethmoid region and c) purulent mucus [1]. Two subtypes of chronic rhinosinusitis comprise distinct clinical syndrome a) Chronic Rhinosinusitis without nasal Polyp (CRSsNP) b) Chronic Rhinosinusitis with nasal polyp (CRSwNP). Approximately 20% of Chronic Rhinosinusitis patients have Asthma and up to 70% of patients with Asthma have chronic rhinosinusitis (CRS) [2,3]. Among severe asthma co-morbidities, one of the most frequent and relevant is chronic rhinosinusitis with nasal polyps (CRSwNP) which affects at least 30% of patients [4].

There is a debate as to what exactly triggers the inflammatory pathways of Chronic Rhinosinusitis (CRS) where infections, superantigens, allergens, biofilms, asthma and aspirin hypersensitivity have all been implicated. The co-existence of CRS and Asthma is explained by the involvement of similar inflammatory pathophysiological pathways in these two conditions, particularly sensitization to allergens and increased serum specific IgE. There is a higher prevalence of positive allergy skin tests and nasal polyposis with most of the evidence pointing to nasal polyps as a manifestation of a systemic disease [5] A possible mechanism for the relationship between severe Chronic Rhino-sinusitis and Asthma has been proposed by Bachert et al, where the production of inflammatory cytokines induces bone marrow to upregulate Eosinophils, mast cells and basophils, which ultimately migrate to the airway mucosa and cause a reactive inflammatory response [6] Currently the success rate of medical management of CRS is approximately 50% [7]The risk of failure in CRS is higher in patients with certain conditions such as nasal polyposis, co-morbid Asthma, Acute Exacerbation of Respiratory Disease (AERD) and allergic fungal rhinosinusitis [8]

Since surgery of CRSwNP, referred to as Functional Endoscopic Sinus Surgery (FESS), is a standard treatment with good functional results in patients resistant to medical treatment and need long term follow up, but most nasal polyps do re-occur with varied post-operative recurrence rate ranging from 13-75% [9] Two of our patients (case 1& 2) have had history multiple surgical interventions (FESS) done due to recurrent nasal polyps.

Molds are considered the third most frequent cause of allergic respiratory disease after dust mites and pollens. Most studies concluded that fungal extracts were not tolerated [10] Alternaria is a risk factor for asthma which activates the innate immune system and enhances lung inflammation, has been linked to airway hyper-responsiveness [11] Alternaria alternata is considered to be a marker of primary sensitization and a ubiquitous saprophytic fungus found in soil and plants, has been described both indoors and outdoors as an allergen associated with Allergic Rhinitis and severe Asthma with fungal sensitization (SAFS) [12]. It is mainly present in the spore wall and respond molecularly to a 30 kDa dimer specific to fungi kingdom. Sensitization to Alt a 1 is identified in more than 90% of patients allergic to A. alternate [13]Alt a 1 is a predominant allergen of the 17 reactive IgE proteins identified in A. alternata, 12 of which are described in the international union of Immunological societies (www.allergen.org). This allergen is released in considerable amount by A. alternata and related species which access the respiratory tract and elicit allergic reaction in these patients.

Omalizumab is a humanized, recombinant antihuman immunoglobulin E (IgE) antibody derived from murine monoclonal antibodies with proven efficacy and effectiveness for adult and paediatric patients with severe allergic asthma [14]. Omalizumab reduces allergen induced responses by decreasing level of free serum IgE and expression of high affinity IgE receptors [15].

The combination of Specific Immunotherapy (SIT) and antiIgE resulted in prolonged inhibition of allergen IgE binding compared with either treatment alone, which might contribute to enhanced clinical efficacy and safety, has a synergistic mode of action and is superior [16,17]. The combined AIT with Omalizumab (a humanized monoclonal antibody) is proven in numerous clinical trials comprising patients with either allergic rhino-conjunctivitis or allergic Asthma. In one study treatment with omalizumab before an intensified rush immunotherapy compared with specific immunotherapy (SIT) alone significantly decreased allergic side effects including anaphylaxis reaction in patients with ragweed induced Seasonal Allergic Rhinitis (SAR) [18] Allergen specific Immunotherapy (SIT) alone induces anti-inflammatory effect, T-cell tolerance by decreasing allergen induced proliferation, alteration of secreted cytokines, stimulation of apoptosis and the production of T-regulatory cells.

In our five cases, two of our cases of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and three cases of Chronic Rhinosinusitis without Nasal Polyps (CRSsNP), were given combined A. alternata Allergen Immunotherapy with Omalizumab resulted in faster and sustained build-up dose, better safety profile, improvement in symptom & medication scoring, PEFR and Immunological scoring.

 

CASE PRESENTATION

Case 1

13year old male with history of Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) and Seasonal Bronchial Asthma since five years was prescribed symptomatic treatment (nasal and inhaled corticosteroids, cetirizine, antibiotic and on & off oral corticosteroids) but had poor relief. He has had history of recurrent episodes of nose block and nasal congestion, progressive loss of smell (hyposmia) and seasonal exacerbations (March-April), underwent surgical intervention thrice (FESS with right ethmoidectomy-year 2011, 2014, 2015) (Figure 1 (a) & (b)) for recurrent nasal polyps. Comprehensive allergy testing by Skin Prick Test (SPT) & Specific IgE was done in 2016.

In-vivo and In-vitro test: (Table 1 (a)) Skin Prick Test (SPT) were positive for Alternaria alternata-10mm, Aspergillus fumigatus-6mm, Candida albicans-4mm, Yeast-3mm.

Specific IgE were positive for Alternaria alternata-93.0 kUA/l,

 

Aspergillus fumigatus-27.7 kUA/l, Candida albicans-25.6 kUA/l, yeast-8.01 kUA/l. Total IgE- 2248 IU/ml, Absolute Eosinophil Count-710 cells/Ul.

Pulmonary Function Tests (2016) were normal FEV1/FVC86.5% with LABA and ICS

Recommendation: Combined Alternaria alternata Subcutaneous Allergen Immunotherapy (SCIT) along with Inj Omalizumab 150mg once a month was started by gradual updosing protocol of build-up phase to achieve MTD (2.5 mg per month maintenance dose) every 4 weeks with supportive therapy for 2 years (Table 1 (b)). His nasal and respiratory symptoms were better controlled with normal Lung function and no variability by PEFR measurement. RCAT (11 Baseline /23), ACT 12 Baseline /21) and SNOT 22 (73 Baseline /17) improved after 1 year. The patient is asymptomatic and under follow-up.

Case 2

24 years old male, known case of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and Co-morbid Bronchial Asthma for the last 11 years. He has had symptoms of nasal obstruction and thick nasal mucus since early childhood. He has been on regular intake of montelukast, cetirizine and indigenous Ayurvedic treatment with no relief. There is history of exacerbation of symptoms of symptoms during change of season (March/April). He consulted an Ear, Nose & Throat specialist and was found to have polypoidal lesion occupying both nasal cavities with yellow and highly viscous mucus. He has had four nasal surgeries during this period and underwent polypectomy and Radiofrequency Sinus Surgery (Figure 2).

Table 1 (b): Duration of Combined Alternaria alternata extract conc. (5mg/ml) for Cluster AIT as per schedule along with Inj Omalizumab (150mg) X 15 days before AIT followed by once in a month for 2 years*.
No. of Visits 1st Visit 2nd Visit 3rd Visit 4th Visit 5th Visit 6th Visit
Cluster Dose AIT (5mg/ ml) Per visit Combined with Inj Omalizumab (150mg)* 0.05/0.05ml @ 60 mts interval 0.1/0.1 ml @ 60 mts interval 0.2/0.2 ml @ 60 mts interval 0.3/0.2 ml @ 60 mts interval 0.5 ml l 0.5 ml (2.5 mg) M.D
Cluster Dose frequency First day 10-12 days s 10-12 days 15-20 days 20-30 days Every 4 weeks

NCCT PNS (2014) done before surgery was suggestive of low density polypoidal mucosal thickening involving bilateral maxillary sinuses (left>right). DNS to right side with mucosal thickening on right side.

Repeat Endoscopy (2017) after 1 year of AIT: revealed mucosal edema.

In-vivo and In-vitro test: (Table 2 (a)) Total IgE-217 IU/ml. Skin Prick Test (SPT) were positive for Alternaria alternata8mm, Aspergillus fumigatus-7mm, Candida albicans-5mm, 5mm, Yeast-4mm. Specific IgE were positive for Alternaria alternata-5.58 kua/l, Aspergillus fumigatus-1.49 kua/l, Candida albicans-1.18 kua/l, Yeast-1.12 kua/l

Pulmonary Function Test (2016): FEV1- 76% and FEV1/ FVC 86%

Recommendation: He was given combined Alternaria alternata Allergen Immunotherapy with effective dose by gradual up-dosing protocol of build-up phase to achieve MTD (2.5 mg per month maintenance dose) along with Inj Omalizumab 150mg once a month with supportive therapy for 1 year (Table 2 (b). His nasal and respiratory symptoms were well controlled. RCAT (13BASELINE/23), ACT(12 BASELINE/22), SNOT 22 (60 BASELINE/16) improved after 1 year. Patient is asymptomatic and on regular follow-up

Case 3

12 years old male, known case of Chronic Rhino-sinusitis without nasal polyp (CRSsNP) and Co-morbid Bronchial Asthma with hypothyroidism, presented with history of recurrent rhinorrhea, nose block, shortness of breath, sneezing, watering from eyes and cough on and off, onset at the age of 2 years. Symptoms were initially mild to moderate but since 6-7 years, exacerbated during months of March-April. He gives h/o hospitalization on 2 occasions for pneumonia at 8 years of age. His vitals were otherwise normal.

In-vivo and In-vitro test: (Table 3 (a)) Total IgE-1196 IU/ml, Absolute Eosinophil Count (AEC)-833 cells/Ul, Skin Prick Test (SPT) were positive for Alternaria alternata-8mm, Aspergillus fumigatus-4mm, Candida albicans-4mm, Yeast-4mm,. Specific IgE were positive for Alternaria alternata-66.6 Kua/L (2018), Candida albicans-1.47 kua/l, Aspergillus fumigatus-4.03 Kua/l, yeast-1.03 kua/l.

Pulmonary Function test (2018)-FEV1-91%, FEV/FVC92.2% (on LABA 12ug and ICS 800ug/ day)

Recommendation: He was given combined Subcutaneous Alternaria alternata Allergen Immunotherapy with effective dose by gradual up-dosing protocol of build-up phase to achieve MTD (2.5 mg per month maintenance dose) along with Inj Omalizumab 150mg once a month with supportive therapy for 2 years (Table 3 (b)). RCAT (10BASELINE/22), ACT (11 BASELINE/21), SNOT 22 (61BASELINE/17) improved after 1 year. Patient is asymptomatic and on regular follow-up. 

Table 4 (b): Duration of Combined Alternaria alternata extract conc. (5mg/ml) for Cluster AIT as per schedule along with Inj Omalizumab (150mg) X 15 days before AIT followed by once in a month for 1 year.*
No. of Visits 1st Visit 2nd Visit 3rd Visit 4th Visit 5th Visit 6th Visit
Cluster Doses (5mg/ml) Per visit with Inj Omalizumab* 0.05/0.05ml @ 60 mts interval 0.1/0.1 ml @ 60 mts interval 0.15/0.15 ml @ 60 mts interval 0.2/0.2 ml @ 60 mts interval 0.4ml 0.4 ml (2mg) M.T.D
Cluster Dose frequency First day 10-12 days 10-12 days 15-20 days 20-30 days Every 4 weeks
M.T.D: Maximum Tolerated Dose; Conc: Concentration; AIT: Allergen Immunotherapy
DISCUSSION

Chronic rhinosinusitis is a prevalent and debilitating disease with nasal polyposis (CRSwNP) & without nasal polyps (CRSsNP). Up to 90% of patients with mild to moderate asthma have abnormal CT findings for the paranasal sinuses and up to 100% of patients with severe asthma have sino-nasal involvement [19]. CRSwNP has a 20-60% association with Co-morbid asthma and has a poorer prognosis with recurrence rate of 38-60% at 12 months [20]. Alternaria alternata is mainly an outdoor aeroallergen, its avoidance as a preventive therapeutic measure is difficult to achieve. Regular cleaning to avoid accumulation of Debris, Dust and Dampness in buildings and to prevent moisture related problems and avoiding indoor smoking are the protective measures that may significantly abate indoor fungal growth. In our 5 patients, the diagnosis of Chronic Rhinosinusitis was defined as per parameters of American Academy of Otolaryngology-Head and Neck Surgery Task Force and diagnosis of Bronchial asthma (mild to moderate persistent) according to the Global Initiative for Asthma 2002 criteria [21]. The combination of Skin Prick Test (SPT) and determination of Specific IgE in the serum is currently recommended for a reliable assessment of sensitization to Alternaria alternata. In children, studies reported 30-38.3% skin test positivity for Alternaria [22]. Our five cases underwent Skin Prick Test (SPT) (Allergo Pharma, Germany/ Greer Lab, USA) to various groups of aeroallergens after giving an informed consent. A positive skin test response was defined as a wheal size >3mm than negative control. Histamine was used a positive control. Specific IgE to Alternaria alternata and other allergens >0.35 IU/ml was based according to ImmunoCAP criteria (Thermo-Fisher, Uppsala, Sweden).

Table 5 (b): Duration of Combined Alternaria alternata extract conc. (5mg/ml) for Cluster AIT as per schedule along with Inj Omalizumab (150mg) X 15 days before AIT followed by once in a month for 1 year.*
No. of Visits 1st Visit 2nd Visit 3rd Visit 4th Visit 5th Visit 6th Visit
Cluster Doses (5mg/ml) Per visit with Inj Omalizumab 150 mg * 0.05/0.05ml @ 60 mts interval 0.1/0.1 ml @ 60 mts interval 0.15/0.15 ml @ 60 mts interval 0.2/0.2 ml @ 60 mts interval 0.4ml 0.4 ml (2mg) M.T.D
Cluster Dose frequency First day 10-12 days 10-12 days 15-20 days 20-30 days Every 4 weeks
M.T.D: Maximum Tolerated Dose; Conc. : concentration; AIT: Allergen Immunotherapy

The allergen vaccine used for SCIT in our cases was prepared by (Greer Lab, USA) of aqueous vaccine method (weight/volume 1:20 concentration). The Maximum Tolerated Dose (MTD) for Allergen specific Immunotherapy (ASIT) was determined and defined as one which produced no systemic adverse reaction [23] AIT was given by gradual up-dosing protocol consisting of two phases; build-up dose and maintenance dose. All five patients received increasing doses starting with 1:200 concentration of Alternaria allergen extract to achieve maximum tolerated dose (Maximum Tolerated Dose 2-2.5 mg of 1:200 concentration) given every 4 weeks, along with Inj Omalizumab 150mg, given 15 days before AIT followed by once in a month for 1 year. Two of our cases (Case 1&3) took combined ASIT with Omalizumab for 2 years while 3 cases (Case 2, 4 & 5) took for 1 year. All of our 5 cases responded well by 12 months and needed no Oral corticosteroids or surgical interference. The improvement was interpreted by the Immunological biomarker [reduction in ratio of specific IgE to Total IgE (Case 1- 4.1% to 2.24%, Case 2- 2.5% to 0.24%, Case 3- 5.5% to 1.7%, Case 4- 3.9% to 1.25%, Case 5- 1.67% to 0.5%) along with 50% reduction in Skin Test reactivity. Changes in the level of Total IgE as perceived are probably not an important biomarker, but there are observational studies that might indicate suppressive effect of SIT on the ratio of specific IgE to Total IgE, as also found in our cases but increase in IgG4 and its role has not been elucidated [24].

In our patients, the severity of symptoms was assessed by (Figure 3):

Increase in the RCAT scoring (Case 1- 11/23, Case 2- 13/23, Case 3- 10/22, Case 4-13/22, Case 5- 11/22. [RCAT scoringRhinitis Control Assessment Test- A 5-point Likert scale where names of categories/ domains include Frequency of nasal congestion, sneezing, and watery eyes; sleep disruption; activity limitation caused by symptoms; and self-rating of symptom control. Scores range from 6 to 30, with higher scores indicating better rhinitis symptom control].

Increase in the ACT scoring- (Case 1- 12/21, Case 2- 12/22, Case 3- 11/21, Case 4- 14/21, Case 5- 12/21). ACT scoring- Asthma Control Test [A 5-point scale which assesses the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control.]

Reduction in the SNOT 22 scoring- (Case 1- 17/13, Case 2- 60/16, Case 3- 61/17, Case 4- 54/14, Case 5- 57/17) SNOT-22- Sino-nasal Outcome Test [A validated patient-reported measure of outcome established to delineate the presence and severity of Sino-nasal disorders. The questions are based on a 0–5 scale] for Quality of life and the dose of medication were scored as (None0, LABA + ICS-1, LABA + ICS + LAMA-2, LAM + ICS + LAMA + OCS-2) patients with Asthma were instructed to measure PEFR and to record it as the best of three tries, twice a day (Morning/ Evening) to look for variability and reversibility [25,26].

We have described in our five cases that a combined therapy of omalizumab and Alternaria alternata Allergen Immunotherapy has an excellent safety profile and efficacy.

CONCLUSION

In our experience, five cases of Chronic Rhinosinusitis with or without Nasal Polyps Co morbid Asthma had significant improvement after combination of A. alternata Subcutaneous Allergen Immunotherapy with Omalizumab. The combination therapy provides faster symptom relief, better lung function and reducing the risk of systemic adverse reactions. This can be explained by prolonged inhibition of IgE binding to receptors on various inflammatory cells. Double-blind placebo-controlled trials are rare and most of the available studies are case reports. We need further studies to recommend this combined treatment of Omalizumab and Allergen Specific Immunotherapy (ASIT) for use in such patients.

ACKNOWLEDGMENT

The authors were assisted in the proof reading and dataanalysis of the manuscript by Dr. Kripashankar Gupta, HeadMedical Affairs, Care Ability.

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Kathuria PC, Rai M, Rai D (2021) Successful management by Combination of Alternaria alternata Subcutaneous Allergen Immunotherapy with Omalizumab in five cases of Chronic Rhinosinusitis with or without Nasal Polyps Co-morbid Asthma. JSM Clin Case Rep 9(1): 1182.

Received : 29 Dec 2020
Accepted : 01 Feb 2021
Published : 05 Feb 2021
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ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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