Treatment for nicotine-induced lung disease using peroxisome proliferator-activated receptor gamma agonists

Abstract

This invention pertains to the discovery that nicotine interrupts molecular signaling between endodermal and mesodermal cells of the lung alveolus. Treatment of the lung with specific molecular agents (e.g., PPAR gamma agonists) can prevent and/or reverse the injury caused by nicotine.

1 - 30 . (canceled) 
     
     
         31 . A kit for treating a patient at risk for or suffering from pulmonary damage associated with the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts, the kit comprising:
 a pharmaceutical composition comprising at least one PPARγ agonist in one or more pharmaceutically-acceptable carrier(s); and   a dosage regimen establishing the amount and frequency of administering the pharmaceutical composition to a patient;   wherein the administering at least one PPARγ agonist prevents, reduces or reverses transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient when the pharmaceutical composition is administered in accordance with the dosing regimen.   
     
     
         32 . The kit of  claim 31 , wherein said PPARγ agonist is a thiozolidinedione. 
     
     
         33 . The kit of  claim 31 , wherein said PPARγ agonist is selected from the group consisting of: rosiglitazone, troglitazone (Resulin), farglitazar, phenylacetic acid, GW590735, GW677954, Avandia, Avandamet (avandia+metformin), ciglitazone, 15 deoxy prostaglandin J2 (15PGJ2), pioglitazone (Actos), 15-deoxy-deltal-2,14 PGD2, MCC-555, and triterpenoids. 
     
     
         34 . The kit of  claim 31 , wherein the pharmaceutical composition is provided in a dosage form selected from the group consisting of: powders, tablets, pills, capsules, lozenges, suppositories, patches, aerosols, inhalers, nasal sprays, injectibles, implantable sustained-release formulations, and lipid complexes. 
     
     
         35 . The kit of  claim 31 , wherein the dosing regimen provides a daily dosing range from about 3 mg/kg to about 100 mg/kg. 
     
     
         36 . The kit of  claim 35 , wherein the daily dosing range is from about 3 mg/kg to about 50 mg/kg. 
     
     
         37 . The kit of  claim 36 , wherein the daily dosing range is from about 3 mg/kg to about 25 mg/kg. 
     
     
         38 . The kit of  claim 33 , wherein the PPARγ agonist is rosiglitazone and wherein the dosing regimen provides a daily dosing range from about 0.1 mg/kg to about 100 mg/kg. 
     
     
         39 . The kit of  claim 38 , wherein the daily dosing range is from about 1 mg/kg to about 50 mg/kg. 
     
     
         40 . The kit of  claim 39 , wherein the daily dosing range is from about 3 mg/kg to about 25 mg/kg. 
     
     
         41 . The kit of  claim 31 , wherein the patient is diagnosed with one or more of the following conditions: asthma, chronic obstructive pulmonary disease, lung cancer or emphysema. 
     
     
         42 . The kit of  claim 31 , wherein the pharmaceutical composition is contraindicated for patients is not diagnosed with or being treated for diabetes, obesity, anorexia, an eating disorder or an appetite disorder. 
     
     
         43 . The kit of  claim 31 , wherein the administering of the PPARγ agonist to the patient prevents the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient. 
     
     
         44 . The kit of  claim 31 , wherein the administering on the PPARγ agonist to the patient reduces the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient. 
     
     
         45 . The kit of  claim 31 , wherein the administering of the PPARγ agonist to the patient reverses the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient. 
     
     
         46 . A method of treating a patient at risk for or suffering from pulmonary damage associated with the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient, the method comprising:
 administering a pharmaceutical composition comprising at least one PPARγ agonist to a patient at risk for or suffering from pulmonary damage associated with the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in a therapeutically effective amount over a dosing regimen;   wherein the administering results in the prevention, reduction or reversal of transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient.   
     
     
         47 . The method of  claim 46 , wherein said PPARγ agonist is a thiozolidinedione. 
     
     
         48 . The method of  claim 46 , wherein said PPARγ agonist is selected from the group consisting of: rosiglitazone, troglitazone (Resulin), farglitazar, muraglitazar, tesaglitazar, phenylacetic acid, GW590735, GW677954, Avandia, Avandamet (avandia+metformin), ciglitazone, 15 deoxy prostaglandin J2 (15PGJ2), pioglitazone (Actos), 15-deoxy-deltal-2,14 PGD2, MCC-555, and triterpenoids. 
     
     
         49 . The method of  claim 46 , wherein said PPARγ agonist is administered via an inhalation route selected from the group consisting of: oral inhalation and nasal inhalation. 
     
     
         50 . The method of  claim 46 , wherein said PPARγ agonist is administered orally. 
     
     
         51 . The method of  claim 46 , wherein said PPARγ agonist is administered systemically. 
     
     
         52 . The method of  claim 46 , wherein the patient is diagnosed with one or more of the following conditions: asthma, chronic obstructive pulmonary disease, lung cancer or emphysema. 
     
     
         53 . The method of  claim 46 , wherein the patient is not diagnosed with or being treated for diabetes, obesity, anorexia, an eating disorder or an appetite disorder. 
     
     
         54 . The method of  claim 46 , wherein the administering results in the prevention of transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient. 
     
     
         55 . The method of  claim 46 , wherein the administering results in the reduction of transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient. 
     
     
         56 . The method of  claim 46 , wherein the administering results in the reversal of transdifferentiation of pulmonary lipofibroblasts to myofibroblasts in the patient.