An Evaluation Criteria of Lower Respiratory Tract Infection Drug Resistant Patients in Need of Alveolar Fibroblasts: Match between Carbon Nanotube Bound Fibroblast Defense and Patient Drug Resistance: NIDHI Criteria

摘要

We report first time a criterion of evaluating the need of choosing alveolar fibroblasts immune to lower respiratory tract infection (LRTI) in LRTI patients who display fatal drug resistance and specific pattern of bacterial infection. Our study was in two phases: 1. Physical characterization of cultured alveolar fibroblast cells customized with carbon nanotube coated delivery system; 2.Gluconeogenesis control and inflammatory characteristics of fibroblasts in prototype 3D lung tissue; 3.A clinical survey of patients with LRTI active infection for presence of bacteria in lungs and clinical symptoms of drug resistance. A simple criteria of "Need of Immune Fibroblast Defense in High LTRI Infection" (NIDHI) was proposed. The hypothesis was fibroblasts regulate and control: 1. gluconeogenesis, inflammatory characteristics of surviving alveolar cells; 2. Fibroblasts exhibit defense against bacteria by blocking its oxygen and glucose; 3. carbon nanotube coated antibiotics along with fibroblasts combine the overall defense. Major points in criteria were: stage 1. Alveolar cells keep intact themselves (hypoxia, apoptosis and metabolic integrity); if all these weaken or fail, stage 2 starts with necrosis, proliferation, tissue structural damage; if it progresses further, stage 3 starts with tumor, pus, abscess, debris (all visible by microsopy)-drug response and resistance starts. The results showed: 1. the microbiology lab data provided a need of matched fibroblast characteristics to enhance the remained alveolar tissue defense and reduce further bacterial drug resistance; 2.initially cytokine induced release is common in response to bacteria/ allergy/ or probably virus injury to aleolar cells. Possibly resistant fibroblast can be helpful in initial phase of disease by enhanced vascularization of lung but later phase of disease remains unknown. Unknown fate of fibroblasts were :1. They experience difficulty (not known) to wrestle with bacteria (unclear which type and drug resistance); 2. Fibroblasts will circumvent in tissue with dying alveolar cells(not known). Major issues of criteria were: l.What difficulties can be there in transferring engineered tissue in human beings?; 2.who are the patients who can be benefited best by this technique? The possible clinical role of customized fibroblasts in clinical research was done by using 3 D artificial lung model (that will simulate patients in stage 2 or 3) enhancing vascularization and use in patients is highlighted. It needs to: step 1: make up of metabolic integrity loss of alveolar cells; step 2: overpowering on bacteria by killing their gluconeogenesis/oxygen supply + saving own resources; step 3: boosting energy supply with help of phagocyte/immune defense to remained alveolar cells; step 4: Match with patients and finally clinical trial. In conclusion, the choice of fibroblasts in LRTI with drug resistance is ideal but a challenge to achieve combined defense by enhanced fibroblast immunity and more controlled antibiotic release at the site.