Efficacy and Safety Evaluation of the Treatment of Allergy Against Cupressaceae and Grasses.

Inclusion criteria

• Written informed consent.
• Aged between 12 and 65, both genders
• Positive suggestive clinical history of intermittent or persistent moderate to severe rhinitis /rhinoconjunctivitis according to ARIA classification, with or without moderate intermittent or persistent asthma,according to GEMA 5.0, due to grass and cupressaceae pollen.
• Subjects with a positive skin prick-test (wheal size \>5 mm diameter) to a standardized mixed extract of grass pollen (Phleum pratense, Holcus lanatus, Dactylis glomerata, Poa pratensis, Festuca elatior, Lolium perenne) or to one of the molecular components of the mixture and to a cupressaceae extract. In addition, the largest diameter of the papules must be greater than or equal to that of the histamine.
• Specific IgE \> 3,5 KU/L , against grass (preferably Phleum pratense) and cupressaceae pollen (InmunoCAP® o Immulite).
• Women of childbearing age (from menarche) must present a urine pregnancy test with a negative result at the time of joining the trial.
• Women of childbearing potential participating in the trial, should commit to using an appropriate method of contraception. Medically acceptable methods of contraception are intrauterine devices placed at least 3 months in advance, surgical sterilization (for example, tubal ligation), barrier methods, or the use of oral contraceptives.
• Subjects capable of complying with the dosing regimen.
• Subjects who own a smartphone for symptom registration and medication.
• Subjects with a negative prick test to coestational pollens. In the case specific IgE is available, the result should be \<3,5 kU/L and without relevant symptomatology
• Subjects with a negative prick test to other aeroallergens (dust mites, epitheliums and fungus). In the case specific IgE is available, the result should be \<3,5 kU/L and without relevant symptomatology.

Exclusion criteria

• Subjects with positive prick test to other aeroallergens except for sensitisation to epithelia with occasional exposure and symptoms.
• Subjects with positive prick test to other aeroallergens except for sensitisation to pollen noncoseasonal with cupressus or grasses.
• Subjects who have received prior immunotherapy in the preceding 5 years for any of the allergens tested or a cross-reactive allergen or are currently receiving immunotherapy with any allergen.
• Subjects in which immunotherapy may be subject to an absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee.
• Subjects with severe or uncontrolled intermittent or persistent asthma, with an FEV1 \<70% with respect to the reference value despite adequate pharmacological treatment at the time of inclusion in the trial. Likewise, subjects with intermittent or persistent rhinitis / rhinoconjunctivitis with severe symptoms in which the suspension of oral or systemic antihistamine treatment is contraindicated.
• Subjects who have previously had a severe secondary reaction during the prick test diagnostic skin test.
• Subjects treated with beta-blockers.
• Clinically unstable subjects at the time of inclusion in the trial (acute asthmatic exacerbation, respiratory infection, febrile process, acute urticaria, etc.).
• Subjects with active chronic urticaria, severe dermographism, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin tests will be performed, or a history of hereditary angioedema.
• Subjects who have any pathology in which adrenaline administration is contraindicated (hyperthyroidism, HTN, heart disease, etc.).
• Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and that may interfere with treatment and follow-up (epilepsy, psychomotor disorder, uncontrolled diabetes, malformations, multioperated patients, kidney disease,).
• Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumor diseases or with a diagnosis of immunodeficiencies.
• Subject whose condition prevents from offering cooperation and/ or who has severe psychiatric disorders.
• Subjects with a known allergy to components of the investigational medicinal product other than the allergen.
• Subjects with lower respiratory diseases other than asthma such as emphysema or bronchiectasis.
• Subjects who are direct relatives of the researchers.
• Pregnant or lactating women.