Pioglitazone and Asthma: A Review of Current Evidence.

OBJECTIVE: This review aims to present existing evidence on the impact of pioglitazone, a thiazolidinedione class anti-diabetic drug, on asthma control and lung function, providing a comprehensive understanding of its potential as a treatment for asthma. DATA SOURCES: The review draws upon data from preclinical animal studies and clinical trials investigating the effects of pioglitazone on asthma, focusing on its role in reducing airway inflammation, hyperreactivity, and remodeling, and its impact on pulmonary function. STUDY SELECTIONS: Relevant studies were selected based on their examination of pioglitazone's therapeutic effects in asthma, including both animal models and clinical trials involving human asthma patients. RESULTS: Animal studies have suggested that pioglitazone could alleviate inflammation, airway hyperreactivity, and airway remodeling, thereby improving pulmonary function in asthma. However, clinical trials have not demonstrated significant therapeutic benefits, with minimal improvements observed in asthma control and lung function, and the presence of notable side effects. CONCLUSION: Despite promising preclinical data, the efficacy of pioglitazone in treating human asthma remains unproven, with safety concerns and limited clinical benefits observed in trials. Further research is needed to assess the safety and effectiveness of pioglitazone in asthma treatment and to explore its impact on other inflammatory mechanisms.

Psychopathology in asthma patients: analysis of demographic and clinical associations.

BACKGROUND: Asthma, a chronic inflammatory condition affecting the airways, significantly impacts both respiratory function and quality of life. Recent studies have highlighted the psychological dimensions of chronic diseases like asthma. Despite growing evidence linking asthma with various psychopathological conditions, comprehensive data remains scarce. AIM: This study aims to explore the psychopathological status of asthma patients and identify demographic and clinical factors associated with higher levels of psychopathological symptoms. METHODS: Data were collected from 42 asthma patients attending the Asthma Outpatient Clinic at the University of Thessaly, Greece. Participants completed a detailed questionnaire on demographics and clinical parameters, along with the Symptoms Checklist-90 (SCL-90) to assess psychological symptoms. RESULTS: The sample included patients with varying asthma severity: 38% with severe asthma and 62% with mild-moderate asthma, with a mean age of 60.8 ± 15.6 years. Results indicated that 23.8% exhibited somatization symptoms, 23.8% showed compulsive behaviors, 33.8% reported interpersonal sensitivity, and 38.1% experienced depression and 38.1% aggressiveness. Additionally, 45.2% struggled with fearful anxiety, 4.8% showed paranoid ideation, and 11.9% had traits of psychoticism. Women had significantly higher psychopathology scores than men. Factors such as longer disease duration, uncontrolled asthma, severe asthma, and comorbid conditions like atopy and gastroesophageal reflux disease (GERD) were linked to higher psychopathological scores. CONCLUSIONS: The study found a high prevalence of psychopathological symptoms among asthma patients. Female gender, prolonged asthma duration, persistent symptoms, comorbid diseases (GERD, atopy) and greater disease severity were significantly associated with higher psychopathology, underscoring the need for integrated mental health care in asthma management.

The Role of Small Airway Disease in Pulmonary Fibrotic Diseases.

Small airway disease (SAD) is a pathological condition that affects the bronchioles and non-cartilaginous airways 2 mm or less in diameter. These airways play a crucial role in respiratory function and are often implicated in various pulmonary disorders. Pulmonary fibrotic diseases are characterized by the thickening and scarring of lung tissue, leading to progressive respiratory failure. We aimed to present the link between SAD and fibrotic lung conditions. The evidence suggests that SAD may act as a precursor or exacerbating factor in the progression of fibrotic diseases. Patients with fibrotic conditions often exhibit signs of small airway dysfunction, which can contribute to worsening respiratory symptoms and decreased lung function. Moreover, individuals with advanced SAD are at a heightened risk of developing fibrotic changes in the lung. The interplay between inflammation, environmental factors, and genetic predisposition further complicates this association. The early detection and management of SAD can potentially mitigate the progression of fibrotic diseases, highlighting the need for comprehensive clinical evaluation and research. This review emphasizes the need to understand the evolving connection between SAD and pulmonary fibrosis, urging further detailed research to clarify the causes and potential treatment between the two entities.

The Role of Osteopontin in Respiratory Health and Disease.

The biological functions of osteopontin (OPN) are diverse and specific to physiological and pathophysiological conditions implicated in inflammation, biomineralization, cardiovascular diseases, cellular viability, cancer, diabetes, and renal stone disease. We aimed to present the role of OPN in respiratory health and disease. OPN influences the immune system and is a chemo-attractive protein correlated with respiratory disease severity. There is evidence that OPN can advance the disease stage associated with its fibrotic, inflammatory, and immune functions. OPN contributes to eosinophilic airway inflammation. OPN can destroy the lung parenchyma through its neutrophil influx and fibrotic mechanisms, linking OPN to at least one of the two major chronic obstructive pulmonary disease phenotypes. Respiratory diseases that involve irreversible lung scarring, such as idiopathic pulmonary disease, are linked to OPN, with protein levels being overexpressed in individuals with severe or advanced stages of the disorders and considerably lower levels in those with less severe symptoms. OPN plays a significant role in lung cancer progression and metastasis. It is also implicated in the pathogenesis of pulmonary hypertension, coronavirus disease 2019, and granuloma generation.

Targeted proteomic analysis dataset of archival core human kidney biopsies to investigate the biology of hypertensive nephropathy.

Hypertensive nephropathy is the second most frequent cause of end-stage renal disease in western societies. In previous experiments in our laboratory with proteomic analysis of renal parenchyma of SHR hypertensive animals, we identified two molecules, namely SGLT2 and CLIC4, associated with the development of hypertension. Here, we apply the methodology of targeted proteomic analysis in kidney biopsies from patients with hypertensive nephropathy to study the role of SGLT2 and CLIC4 in the pathogenesis of the disease. Relative quantification data of SGLT2 and CLIC4 via means of targeted proteomic analysis in human kidney biopsies from hypertensive patients and normotensive controls are reported. In addition, validation data of the proteomic results via immunofluorescence are presented. Renal tissue biopsies (N = 17) from archival material of patients with hypertensive nephropathy and normotensive controls were used. Targeted proteomic analysis was performed using the method: ``Parallel Reaction Monitoring'' (PRM) in renal parenchyma of hypertensive and normotensive patients for the selective identification of SGLT2 and CLIC4 and the relative quantification of their expression using proteotypic peptides for each protein. The expression of SGLT2 molecule was also confirmed by immunofluorescence followed by quantification of fluorescence intensity. According to PRM, the SGLT2 protein was found with reduced and the CLIC4 protein with increased expression levels in hypertensive patients compared to normotensive controls. Comparison of representative immunofluorescence images confirmed a decrease in the expression of SGLT2 in the brush border of proximal tubular epithelial cells in hypertensive patients. Our data show changes in the tubular compartment of the kidney and especially in the proximal tubules associated with the hypertensive nephropathy. The clinical significance of these findings should be further explored for the discovery and/or confirmation of novel therapeutic approaches and biomarkers in the development of hypertensive kidney disease.

Chloride Intracellular Channel 4 Overexpression in the Proximal Tubules of Kidneys from the Spontaneously Hypertensive Rat: Insight from Proteomic Analysis.

BACKGROUND: Hypertensive nephropathy, a leading cause of declining kidney function, is a multifactorial process not well understood. In order to elucidate biological processes and identify novel macromolecular components crucially involved in the process of kidney damage, the application of system biology approaches, like proteomics, is required. METHODS: Proteomic studies were performed using the renal parenchyma of spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls. Animals were sacrificed at early time intervals (6, 13, and 20 weeks after birth), the renal tissue extract was subjected to two-dimensional gel electrophoresis, differential expressed proteins were identified, and altered pathways were evaluated. One specific protein, chloride intracellular channel 4 (CLIC4), not implicated so far in the development of hypertension and nephrosclerosis, was further studied by Western blotting, immunohistochemistry and immunofluorescence. RESULTS: Proteomic analysis identified several pathways/processes and organelles (mitochondria) as being affected from the early stages of hypertension. CLIC4 was overexpressed in SHR at all 3 time intervals examined. This finding was confirmed by Western blotting and by immunohistochemistry and immunofluorescence; these morphological techniques demonstrated that CLIC4 was almost exclusively localized at the apical surface of the proximal tubular epithelial cells. CONCLUSIONS: Our studies provide evidence that major changes occur in the renal parenchyma from early stages of the development of hypertension. The overexpression of CLIC4 suggests that alterations in the proximal tubular compartment during hypertension should be further examined and that CLIC4 may be a useful early marker of renal tubular alterations due to elevated blood pressure.

Drosophila oogenesis as a bio-marker responding to EMF sources.

The model biological organisms Drosophila melanogaster and Drosophila virilis have been utilized to assess effects on apoptotic cell death of follicles during oogenesis and reproductive capacity (fecundity) decline. A total of 280 different experiments were performed using newly emerged flies exposed for short time daily for 3-7 d to various EMF sources including: GSM 900/1800 MHz mobile phone, 1880-1900 MHz DECT wireless base, DECT wireless handset, mobile phone-DECT handset combination, 2.44 GHz wireless network (Wi-Fi), 2.44 GHz blue tooth, 92.8 MHz FM generator, 27.15 MHz baby monitor, 900 MHz CW RF generator and microwave oven's 2.44 GHz RF and magnetic field components. Mobile phone was used as a reference exposure system for evaluating factors considered very important in dosimetry extending our published work with D. melanogaster to the insect D. virilis. Distance from the emitting source, the exposure duration and the repeatability were examined. All EMF sources used created statistically significant effects regarding fecundity and cell death-apoptosis induction, even at very low intensity levels (0.3 V/m blue tooth radiation), well below ICNIRP's guidelines, suggesting that Drosophila oogenesis system is suitable to be used as a biomarker for exploring potential EMF bioactivity. Also, there is no linear cumulative effect when increasing the duration of exposure or using one EMF source after the other (i.e. mobile phone and DECT handset) at the specific conditions used. The role of the average versus the peak E-field values as measured by spectrum analyzers on the final effects is discussed.