Methods for treating inflammatory conditions of the lungs

Abstract

The present invention relates to methods for treatment or prevention of asthma, mild intermittent asthma, mild persistent asthma, moderate persistent asthma, severe persistent asthma, eosinophilic asthma, neutrophilic asthma, steroid refractory asthma, status asthmaticus, pneumonia, bronchiectasis, COPD, sarcoidosis, and lung cancer based on reducing airway hyper responsiveness, increasing pulmonary compliance, reducing lung inflammation, reducing inflammatory cell count in bronchoalveolar fluid and reducing cytokine production by administration of a mammalian α- and/or β-defensin.

1 - 28 . (canceled) 
     
     
         29 . A method of treatment of asthma, bronchiectasis, chronic obstructive pulmonary disorder (COPD) or emphysema, the method comprising oral or intrapulmonary administration of at least one defensin selected from the group consisting of HD5, HD6, hBD1, hBD2, hBD3, hBD4, and hBD2 N-terminally truncated by 1-4 amino acids to a subject in need thereof. 
     
     
         30 . The method of  claim 29 , wherein said asthma is mild intermittent asthma, mild persistent asthma, moderate persistent asthma, severe persistent asthma, eosinophilic asthma, neutrophilic asthma, steroid refractory asthma, or status asthmaticus. 
     
     
         31 . The method of  claim 29 , wherein said asthma is steroid refractory. 
     
     
         32 . The method according to  claim 29 , wherein the administration is oral. 
     
     
         33 . The method according to  claim 29 , wherein said defensin is hBD1, hBD2, hBD3, hBD4, or N-terminally truncated hBD2 by 1-4 amino acids. 
     
     
         34 . The method according to  claim 29 , wherein said defensin is hBD2 or hBD2 N-terminally truncated by 1-4 amino acids. 
     
     
         35 . The method according to  claim 29 , wherein at least two defensins are administered. 
     
     
         36 . The method according to  claim 35 , wherein said at least two defensins are hBD2 and HD5. 
     
     
         37 . The method according to  claim 29 , wherein said method increases pulmonary compliance, reduces airway hyper responsiveness, or increases peak expiratory flow in the subject. 
     
     
         38 . The method according to  claim 29 , wherein said method results in increasing gene richness, increasing the number of phylae, increasing butyrate production and/or tryptophan production, or decreasing acetate production of or from lung microbiota. 
     
     
         39 . The method according to  claim 29 , wherein the subject has
 a. asthmatic symptoms more than 2 times per week;   b. asthmatic attacks at varying intensity;   c. asthmatic symptoms at night more than 2 times per month;   d. a forced expiratory volume at 1 second (FEV1) less than 80; or   e. a peak expiratory flow rate (PEFR) with a variability of more than 20%.   
     
     
         40 . The method according to  claim 29 , wherein the defensin is administered in combination with one or more glucocorticoids, β-agonists, leukotriene receptor antagonists, theophylline, antibiotics, rifaximin, immunosuppressants, chemo- or immune therapy, prebiotics, probiotics, tryptophane, fatty acids, HNP-1, HNP-2, HNP-3, HNP-4, cathelicidin, lactoferrin, lactoferricin, lysozyme, fecal transplants or any combination thereof. 
     
     
         41 . The method according to  claim 29 , wherein said defensin is administered at a dosage of 0.1 mg to 10 mg defensin/kg per day. 
     
     
         42 . The method according to  claim 29 , wherein said defensin is administered every other day. 
     
     
         43 . The method according to  claim 29 , wherein said defensin is administered daily. 
     
     
         44 . The method according to  claim 29 , wherein the treatment alleviates at least one continuous asthmatic symptom. 
     
     
         45 . The method according to  claim 29 , wherein said intrapulmonary administration is intratracheal, intrabronchial, or bronchio-alveolar. 
     
     
         46 . A method of treatment of steroid refractory asthma, the method comprising oral administration of hBD2 to a subject in need thereof. 
     
     
         47 . A method of treatment of COPD, the method comprising oral administration of hBD2 to a subject in need thereof.