Idiopathic pulmonary fibrosis landscapes: looking glass from pathology to therapy.

Idiopathic pulmonary fibrosis (IPF) is a rare chronic and ultimately fatal disease resulting in an aberrant scarring and thickening of lung tissue. Molecular pathogenetic mechanisms of IPF are still unknown and till now no effective therapy is known to really improve disease's outcome. A deeper understanding of IPF biology is now mandatory to clarify IPF origin in order to identify actionable targets. Here we discuss and analyze the data presented by a recent paper published by De Pianto et al. on the prestigious respiratory journal Thorax. The work is focused on how gene expression analysis can be applied to stratify IPF cases based on their risk of disease progression. Moreover they tried to match genetic and phenotypic profiles in order to predict therapeutic response and patients' prognosis.

Idiopathic pulmonary fibrosis landscapes: looking glass from pathology to therapy.

Idiopathic pulmonary fibrosis (IPF) is a rare chronic and ultimately fatal disease resulting in an aberrant scarring and thickening of lung tissue. Molecular pathogenetic mechanisms of IPF are still unknown and till now no effective therapy is known to really improve disease's outcome. A deeper understanding of IPF biology is now mandatory to clarify IPF origin in order to identify actionable targets. Here we discuss and analyze the data presented by a recent paper published by De Pianto et al. on the prestigious respiratory journal Thorax. The work is focused on how gene expression analysis can be applied to stratify IPF cases based on their risk of disease progression. Moreover they tried to match genetic and phenotypic profiles in order to predict therapeutic response and patients' prognosis.

Viral Infections in lung transplant recipients: devils or trolls?

Lung transplantation is a therapeutic option for end stage lung diseases. One of the most important topics in transplant management is the role of viral infections in chronic lung allograft dysfunction (CLAD) and in particular in acute rejection (AR). This review arise from a recent study BY Brideaux et al. that offers the opportunity to investigate deeply the incidence, risk factors, symptomatology and clinical outcome of respiratory viral infections. Although most respiratory viral infections cause self-limited upper respiratory diseases, lung transplant recipients (LTRs) are particularly prone to develop complications. The absence of symptoms is a pivotal problem in managing these patients as it can depend on absence of active replication or on the effect of immunosuppressive regimen. In one word viruses can be just passengers or aggressive drivers in a facilitated environment, and the potential damage is completely different, as the management. PCR samplings give us an idea of the presence but not the certainty of the activity of viruses, and this is another common problem in reading data. In Herpes Virus infections this problem can be overtaken by studying biological samples and immune response, balancing the presence (PCR) and the activity (shell vial) of viruses with specific immune response (elispot). In fact viral presence doesn't mean activity and activity doesn't mean pathology in case of competent immune response. All these data can be matched in every single patient and managed by a tailored approach, either monitoring or treating.

Idiopathic pulmonary fibrosis clustering based on cilium gene expression: profiling a new paradigm.

Idiopathic pulmonary fibrosis (IPF), the commonest form of the interstitial lung diseases identifies a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults, and limited to the lungs. IPF represents an unsolved health problem with an urgent medical need due to lack of effective therapies. Although precise IPF etiology remains elusive, during the past decade there has been a shift away from the pathogenetic theory of generalized inflammation progressing to a paradigm of disordered fibroproliferation and alveolar epithelial cell function. A better understanding of the molecular mechanisms driving IPF fibroblasts proliferation is mandatory to provide insights into the pathogenesis, and to identify highly reproducible biomarkers for disease onset and progression. In this review we aim to discuss and analyze the findings recently published by Yang et al. on Thorax, which reported a strong molecular signature as-sociated with the expression of cilium genes that divides IPF/ usual interstitial pneumonia into two subtypes, one with increased cilium gene expression and one with low expression of cilium genes. The study presents a number of methodology limitations, mainly related to samples characterization and to a general overstatement of the conclusions from class clustering analysis. Nevertheless, the study clearly demonstrates ­ for the first time ­ that the cilium apparatus is activated in microscopic honeycombing. In such setting, cilia are likely to act as signaling "machine" which cooperates in promoting proliferative and regenerative cellular processes. Although preliminary, these results sustain a rationale to develop further investigations to confirm the impact of cilium gene expression in IPF with the final perspective of therapeutic intervention.

Noneosinophilic asthma in children: relation with airway remodelling.

Noneosinophilic asthma is increasingly recognised as an important clinical-pathological phenotype in adults. However, this entity has scarcely been investigated in children. In particular, it is unknown whether airway remodelling would develop in children with non-eosinophilic asthma to the same degree as in children with eosinophilic disease. We analysed bronchial biopsies from 80 children undergoing bronchoscopy for appropriate clinical indications: 21 with noneosinophilic asthma, 34 with eosinophilic asthma and 25 control children. Features of airway remodelling - basement membrane thickening, epithelial loss and angiogenesis - and immune activation - inflammatory infiltrate, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-ß, TGF-ß receptor type II - were quantified by histology and immunohistochemistry. The main components of airway remodelling were present in children with noneosinophilic asthma just as in those with eosinophilic disease. Indeed, compared with control children, both noneosinophilic and eosinophilic asthmatic children had thickened basement membrane, increased epithelial loss and higher number of vessels. Moreover, in both groups of asthmatics, expression of IL-4 and IL-5 was increased, while that of TGF-ß receptor type II was reduced, compared with controls. This study demonstrates that structural changes typical of asthma develop in asthmatic children even in the absence of a prominent eosinophilic infiltrate, indicating that other mechanisms, besides eosinophilic inflammation, may promote airway remodelling early in life.

High-resolution CT of nontuberculous mycobacteria pulmonary infection in immunocompetent, non-HIV-positive patients.

PURPOSE: The objective of this study was to demonstrate that nontuberculous mycobacteria (NTM) pulmonary infections are not so infrequent and that the diagnosis may be suggested on the basis of the high-resolution computed tomography (HRCT) pattern alone. MATERIALS AND METHODS: We retrospectively reviewed HRCT scans of 29 patients (9 men, 18 women; mean age 63 years, range 38-88 years) with positive culture from bronchial wash. Mycobacterium avium complex (MAC) was present in all (with the exception of one in whom the NTM was indistinct). In six patients, MAC was associated with M. chelonae, M. kansasii, M. fortuitum or M. xenopi. In one of these patients, MAC was associated with both M. fortuitum and M. chelonae. All patients had had nonspecific symptoms of pulmonary infection for a time ranging from 6 months to 12 years. Previous tuberculous infection was present in five patients (18.5%). Eleven patients had other pulmonary diseases (40.8%), and 12 had associated systemic diseases (44.4%). RESULTS: HRCT findings were apical fibrotic scarring (n=8; 29.6%), consolidations (n=16; 59.2%), single/multiple nodules >1 cm (n=8, multiple; 29.6%), cavitations (n=7; 25.9%), ground glass appearance (n=3; 11.1%), reticular/reticulonodular pattern (n=6; 22.2%), bronchiectasis (n=25; 92.5%), centrilobular nodules (tree in bud) (n=24; 88.8%), air trapping (n=8; 29.6%), lymphadenopathy >1 cm, also with calcification (n=13, 3 with calcification; 48.1%) and pleural effusion (n=2; 7.4%). In 3/7 patients with nodules >1 cm and with cavitations, the "feeding bronchus sign" (a patent bronchus running into a cavitation) was present. Lesions were in the upper lobes in 23 (85.1%), middle lobe/lingula in 25 (92.5%) and lower lobes in 18 (66.6%) patients. The findings were diffuse in 13 (48.1%) cases and patchy in 17 (62.9%). CONCLUSIONS: HRCT findings are essential for the diagnosis of NTM pulmonary infection. The presence of bronchiectasis, cavitary nodules with feeding bronchus sign and tree-in-bud nodules in the middle lobe and lingula are suggestive of NTM infection, thus assisting the physician in the diagnostic workup of these patients.

Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis.

The aim of the study was to investigate the expression of basic fibroblast growth factor (bFGF) and its receptor, fibroblast growth factor receptor (FGFR)-1, in the central airways of smokers with chronic bronchitis. The lobar bronchi from 17 subjects undergoing thoracotomy for solitary nodules were examined. All had a history of cigarette smoking, nine had symptoms of chronic bronchitis and airflow limitation, and eight were asymptomatic with normal lung function. Using immunohistochemical methods, bFGF and FGFR-1 expression in the total airway wall and the different airway compartments, i.e. bronchial glands, submucosal vessels and smooth muscle, was quantified. Moreover, to investigate the role of bFGF in angiogenesis, the number of submucosal vessels was quantified. Smokers with chronic bronchitis had an increased bFGF expression in the total airway wall compared with asymptomatic smokers, which was mainly due to bFGF upregulation in bronchial glands. By contrast, the expression of FGFR-1 and the number of submucosal vessels was similar in the two groups of subjects examined. In conclusion, smokers with chronic bronchitis have an increased expression of basic fibroblast growth factor in the central airways, which is mainly due to an increased expression in bronchial glands, suggesting the involvement of this growth factor in the pathogenesis of chronic bronchitis.