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Special Issue "Lung Diseases: Chronic Respiratory Infections"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2017).

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Special Issue Editor

Prof. Dr. Francesco B. Blasi
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Guest Editor
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, IRCCS Fondazione Ospedale Maggiore Policlinico Cà Granda, Milan 20122, Italy
Interests: pneumonia; COPD; bronchiectasis; cystic fibrosis; lung transplantation
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Special Issue Information

Dear Colleagues,

Both chronic and acute infections play a significant role in the pathogenesis and clinical course of chronic obstructive pulmonary disease (COPD) and both cystic fibrosis (CF) and non-CF bronchiectasis. There is also specific evidence that chronic infection, even in the absence of acute infection, has an influence on the manifestations and disease course. The infections found in COPD, CF, and bronchiectasis share a number of clinical similarities, the most striking of which are bacterial persistence despite the use of antibiotics and antibiotic resistance.

In the last two decades, antibiotic resistance rate has increased dramatically and poses serious threats for patients and the public health. There are different reasons for this increase in resistance, but the overuse of antibiotics in the community is certainly the most prominent. On the other hand, chronic use of antibiotics in chronic diseases like COPD, CF and bronchiectasis is also potentially associated to an increase in MDR pathogens. During the last decade, a growing interest has been raised in evaluating nontuberculous mycobacteria’s role in chronic respiratory diseases like bronchiectasis.

Prof. Dr. Francesco B. Blasi
Guest Editor

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Keywords

  • Respiratory infections
  • Bronchiectasis
  • Non-Tuberculous Mycobacteria
  • Nebulised antibiotic
  • COPD

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Editorial

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Open AccessEditorial
Lung Diseases: Chronic Respiratory Infections
Int. J. Mol. Sci. 2018, 19(10), 3051; https://doi.org/10.3390/ijms19103051 - 07 Oct 2018
Cited by 1
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available

Research

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Open AccessArticle
Targeting the Bacterial Cytoskeleton of the Burkholderia cepacia Complex for Antimicrobial Development: A Cautionary Tale
Int. J. Mol. Sci. 2018, 19(6), 1604; https://doi.org/10.3390/ijms19061604 - 30 May 2018
Cited by 3
Abstract
Burkholderia cepacia complex (BCC) bacteria are a group of opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult, due to the inherent and acquired multidrug resistance of BCC. There is a pressing need to find [...] Read more.
Burkholderia cepacia complex (BCC) bacteria are a group of opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult, due to the inherent and acquired multidrug resistance of BCC. There is a pressing need to find new bacterial targets for antimicrobials. Here, we demonstrate that the novel compound Q22, which is related to the bacterial cytoskeleton destabilising compound A22, can reduce the growth rate and inhibit growth of BCC bacteria. We further analysed the phenotypic effects of Q22 treatment on BCC virulence traits, to assess its feasibility as an antimicrobial. BCC bacteria were grown in the presence of Q22 with a broad phenotypic analysis, including resistance to H2O2-induced oxidative stress, changes in the inflammatory potential of cell surface components, and in-vivo drug toxicity studies. The influence of the Q22 treatment on inflammatory potential was measured by monitoring the cytokine responses of BCC whole cell lysates, purified lipopolysaccharide, and purified peptidoglycan extracted from bacterial cultures grown in the presence or absence of Q22 in differentiated THP-1 cells. BCC bacteria grown in the presence of Q22 displayed varying levels of resistance to H2O2-induced oxidative stress, with some strains showing increased resistance after treatment. There was strain-to-strain variation in the pro-inflammatory ability of bacterial lysates to elicit TNFα and IL-1β from human myeloid cells. Despite minimal toxicity previously shown in vitro with primary CF cell lines, in-vivo studies demonstrated Q22 toxicity in both zebrafish and mouse infection models. In summary, destabilisation of the bacterial cytoskeleton in BCC, using compounds such as Q22, led to increased virulence-related traits in vitro. These changes appear to vary depending on strain and BCC species. Future development of antimicrobials targeting the BCC bacterial cytoskeleton may be hampered if such effects translate into the in-vivo environment of the CF infection. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Aspergillus fumigatus Detection and Risk Factors in Patients with COPD–Bronchiectasis Overlap
Int. J. Mol. Sci. 2018, 19(2), 523; https://doi.org/10.3390/ijms19020523 - 09 Feb 2018
Cited by 7
Abstract
The role of Aspergillus fumigatus in the airways of chronic obstructive pulmonary disease (COPD) patients with bronchiectasis is currently unclear. We searched for a sensitive and noninvasive method for A. fumigatus detection in the sputum of COPD patients and addressed potential risk factors [...] Read more.
The role of Aspergillus fumigatus in the airways of chronic obstructive pulmonary disease (COPD) patients with bronchiectasis is currently unclear. We searched for a sensitive and noninvasive method for A. fumigatus detection in the sputum of COPD patients and addressed potential risk factors for its presence. Induced sputum samples of 18 COPD patients and 17 COPD patients with bronchiectasis were analyzed for the presence of A. fumigatus by culture, galactomannan detection, and PCR. Of the patients with COPD–bronchiectasis overlap, 23.5% had a positive culture for A. fumigatus versus 10.5% of COPD patients without bronchiectasis (p = 0.39). The median sputum galactomannan optical density index was significantly higher in patients with COPD and bronchiectasis compared with patients with COPD alone (p = 0.026) and ranged between the levels of healthy controls and A. fumigatus-colonized cystic fibrosis patients. Both the presence of bronchiectasis and the administration of systemic corticosteroids were associated with sputum galactomannan (p = 0.0028 and p = 0.0044, respectively) and showed significant interaction (p interaction = 0.022). PCR for Aspergillus was found to be a less sensitive method, but was critically dependent on the extraction technique. The higher sputum galactomannan levels suggest a more abundant presence of A. fumigatus in the airways of patients with COPD–bronchiectasis overlap compared with patients with COPD without bronchiectasis, particularly when systemic corticosteroids are administered. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in Atherosclerosis Prone ApoE−/− Mice Following Regular Exposure to Cigarette Smoke
Int. J. Mol. Sci. 2018, 19(2), 343; https://doi.org/10.3390/ijms19020343 - 24 Jan 2018
Cited by 3
Abstract
Chronic obstructive pulmonary disease (COPD) is associated with severe chronic inflammation that promotes irreversible tissue destruction. Moreover, the most broadly accepted cause of COPD is exposure to cigarette smoke. There is no effective cure and significantly, the mechanism behind the development and progression [...] Read more.
Chronic obstructive pulmonary disease (COPD) is associated with severe chronic inflammation that promotes irreversible tissue destruction. Moreover, the most broadly accepted cause of COPD is exposure to cigarette smoke. There is no effective cure and significantly, the mechanism behind the development and progression of this disease remains unknown. Our laboratory has demonstrated that Bruton’s tyrosine kinase (Btk) is a critical regulator of pro-inflammatory processes in the lungs and that Btk controls expression of matrix metalloproteinase-9 (MMP-9) in the alveolar compartment. For this study apolipoprotein E null (ApoE−/−) mice were exposed to SHS to facilitate study in a COPD/atherosclerosis comorbidity model. We applied two types of treatments, animals received either a pharmacological inhibitor of Btk or MMP-9 specific siRNA to minimize MMP-9 expression in endothelial cells or neutrophils. We have shown that these treatments had a protective effect in the lung. We have noted a decrease in alveolar changes related to SHS induced inflammation in treated animals. In summary, we are presenting a novel concept in the field of COPD, i.e., that Btk may be a new drug target for this disease. Moreover, cell specific targeting of MMP-9 may also benefit patients affected by this disease. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Synthesized Heparan Sulfate Competitors Attenuate Pseudomonas aeruginosa Lung Infection
Int. J. Mol. Sci. 2018, 19(1), 207; https://doi.org/10.3390/ijms19010207 - 09 Jan 2018
Cited by 2
Abstract
Several chronic respiratory diseases are characterized by recurrent and/or persistent infections, chronic inflammatory responses and tissue remodeling, including increased levels of glycosaminoglycans which are known structural components of the airways. Among glycosaminoglycans, heparan sulfate (HS) has been suggested to contribute to excessive inflammatory [...] Read more.
Several chronic respiratory diseases are characterized by recurrent and/or persistent infections, chronic inflammatory responses and tissue remodeling, including increased levels of glycosaminoglycans which are known structural components of the airways. Among glycosaminoglycans, heparan sulfate (HS) has been suggested to contribute to excessive inflammatory responses. Here, we aim at (i) investigating whether long-term infection by Pseudomonas aeruginosa, one of the most worrisome threat in chronic respiratory diseases, may impact HS levels, and (ii) exploring HS competitors as potential anti-inflammatory drugs during P. aeruginosa pneumonia. P. aeruginosa clinical strains and ad-hoc synthesized HS competitors were used in vitro and in murine models of lung infection. During long-term chronic P. aeruginosa colonization, infected mice showed higher heparin/HS levels, evaluated by high performance liquid chromatography-mass spectrometry after selective enzymatic digestion, compared to uninfected mice. Among HS competitors, an N-acetyl heparin and a glycol-split heparin dampened leukocyte recruitment and cytokine/chemokine production induced by acute and chronic P. aeruginosa pneumonia in mice. Furthermore, treatment with HS competitors reduced bacterial burden during chronic murine lung infection. In vitro, P. aeruginosa biofilm formation decreased upon treatment with HS competitors. Overall, these findings support further evaluation of HS competitors as a novel therapy to counteract inflammation and infection during P. aeruginosa pneumonia. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Environmental Burkholderia cenocepacia Strain Enhances Fitness by Serial Passages during Long-Term Chronic Airways Infection in Mice
Int. J. Mol. Sci. 2017, 18(11), 2417; https://doi.org/10.3390/ijms18112417 - 14 Nov 2017
Cited by 4
Abstract
Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF) patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from [...] Read more.
Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF) patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from clinical strains in some pathogenic traits. Here, we investigated the ability of the environmental B. cenocepacia Mex1 strain, isolated from the maize rhizosphere, to persist and increase its virulence after serial passages in a mouse model of chronic infection. B. cenocepacia Mex1 strain, belonging to the recA lineage IIIA, was embedded in agar beads and challenged into the lung of C57Bl/6 mice. The mice were sacrificed after 28 days from infection and their lungs were tested for bacterial loads. Agar beads containing the pool of B. cenocepacia colonies from the four sequential passages were used to infect the mice. The environmental B. cenocepacia strain showed a low incidence of chronic infection after the first passage; after the second, third and fourth passages in mice, its ability to establish chronic infection increased significantly and progressively up to 100%. Colonial morphology analysis and genetic profiling of the Mex1-derived clones recovered after the fourth passage from infected mice revealed that they were indistinguishable from the challenged strain both at phenotypic and genetic level. By testing the virulence of single clones in the Galleria mellonella infection model, we found that two Mex1-derived clones significantly increased their pathogenicity compared to the parental Mex1 strain and behaved similarly to the clinical and epidemic B. cenocepacia LMG16656T. Our findings suggest that serial passages of the environmental B. cenocepacia Mex1 strain in mice resulted in an increased ability to determine chronic lung infection and the appearance of clonal variants with increased virulence in non-vertebrate hosts. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Polydeoxyribonucleotide Ameliorates Lipopolysaccharide-Induced Lung Injury by Inhibiting Apoptotic Cell Death in Rats
Int. J. Mol. Sci. 2017, 18(9), 1847; https://doi.org/10.3390/ijms18091847 - 24 Aug 2017
Cited by 6
Abstract
Lung injury is characterized by diffuse lung inflammation, alveolar-capillary destruction, and alveolar flooding, resulting in respiratory failure. Polydexyribonucleotide (PDRN) has an anti-inflammatory effect, decreasing inflammatory cytokines, and suppressing apoptosis. Thus, we investigated its efficacy in the treatment of lung injury, which was induced [...] Read more.
Lung injury is characterized by diffuse lung inflammation, alveolar-capillary destruction, and alveolar flooding, resulting in respiratory failure. Polydexyribonucleotide (PDRN) has an anti-inflammatory effect, decreasing inflammatory cytokines, and suppressing apoptosis. Thus, we investigated its efficacy in the treatment of lung injury, which was induced in rats using lipopolysaccharide (LPS). Rats were randomly divided into three groups according to sacrifice time, and each group split into control, lung injury-induced, and lung injury-induced + PDRN-treated groups. Rats were sacrificed 24 h and 72 h after PDRN administration, according to each group. Lung injury was induced by intratracheal instillation of LPS (5 mg/kg) in 0.2 mL saline. Rats in PDRN-treated groups received a single intraperitoneal injection of 0.3 mL distilled water including PDRN (8 mg/kg), 1 h after lung injury induction. Percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive, cleaved caspase-3-, -8-, and -9-positive cells, the ratio of Bcl-2-associated X protein (Bax) to B-cell lymphoma 2 (Bcl-2), and expressions of inflammatory cytokines (tumor necrosis factor-α, interleukin-6) were decreased by PDRN treatment in the LPS-induced lung injury rats. Therefore, treatment with PDRN reduced lung injury score. This anti-apoptotic effect of PDRN can be ascribed to the enhancing effect of PDRN on adenosine A2A receptor expression. Based on these results, PDRN might be considered as a new therapeutic agent for the treatment of lung injury. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease
Int. J. Mol. Sci. 2017, 18(8), 1654; https://doi.org/10.3390/ijms18081654 - 29 Jul 2017
Cited by 8
Abstract
In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which [...] Read more.
In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Immunological Roles of Elevated Plasma Levels of Matricellular Proteins in Japanese Patients with Pulmonary Tuberculosis
Int. J. Mol. Sci. 2017, 18(1), 19; https://doi.org/10.3390/ijms18010019 - 22 Dec 2016
Cited by 9
Abstract
Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex [...] Read more.
Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI), and 19 healthy controls (HCs) from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs). Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB) strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively) than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessArticle
Characterizing Non-Tuberculous Mycobacteria Infection in Bronchiectasis
Int. J. Mol. Sci. 2016, 17(11), 1913; https://doi.org/10.3390/ijms17111913 - 16 Nov 2016
Cited by 24
Abstract
Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) [...] Read more.
Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic P. aeruginosa infection; chronic infection due to bacteria other than P. aeruginosa. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic P. aeruginosa infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a “tree-in-bud” pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Review

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Open AccessReview
Fungi in Bronchiectasis: A Concise Review
Int. J. Mol. Sci. 2018, 19(1), 142; https://doi.org/10.3390/ijms19010142 - 04 Jan 2018
Cited by 8
Abstract
Although the spectrum of fungal pathology has been studied extensively in immunosuppressed patients, little is known about the epidemiology, risk factors, and management of fungal infections in chronic pulmonary diseases like bronchiectasis. In bronchiectasis patients, deteriorated mucociliary clearance—generally due to prior colonization by [...] Read more.
Although the spectrum of fungal pathology has been studied extensively in immunosuppressed patients, little is known about the epidemiology, risk factors, and management of fungal infections in chronic pulmonary diseases like bronchiectasis. In bronchiectasis patients, deteriorated mucociliary clearance—generally due to prior colonization by bacterial pathogens—and thick mucosity propitiate, the persistence of fungal spores in the respiratory tract. The most prevalent fungi in these patients are Candida albicans and Aspergillus fumigatus; these are almost always isolated with bacterial pathogens like Haemophillus influenzae and Pseudomonas aeruginosa, making very difficult to define their clinical significance. Analysis of the mycobiome enables us to detect a greater diversity of microorganisms than with conventional cultures. The results have shown a reduced fungal diversity in most chronic respiratory diseases, and that this finding correlates with poorer lung function. Increased knowledge of both the mycobiome and the complex interactions between the fungal, viral, and bacterial microbiota, including mycobacteria, will further our understanding of the mycobiome’s relationship with the pathogeny of bronchiectasis and the development of innovative therapies to combat it. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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Open AccessReview
The Lung Microbiome in Idiopathic Pulmonary Fibrosis: A Promising Approach for Targeted Therapies
Int. J. Mol. Sci. 2017, 18(12), 2735; https://doi.org/10.3390/ijms18122735 - 16 Dec 2017
Cited by 9
Abstract
This review focuses on the role of the lung microbiome in idiopathic pulmonary fibrosis. Although historically considered sterile, bacterial communities have now been well documented in lungs both in healthy and pathological conditions. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial [...] Read more.
This review focuses on the role of the lung microbiome in idiopathic pulmonary fibrosis. Although historically considered sterile, bacterial communities have now been well documented in lungs both in healthy and pathological conditions. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. Existing published data suggesting that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. Taken altogether, published literature suggests that the lung microbiome might serve in the future as a prognostic biomarker, a therapeutic target, and/or provide an explanation for disease pathogenesis in IPF. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
Open AccessReview
Chronic Respiratory Infection in Patients with Chronic Obstructive Pulmonary Disease: What Is the Role of Antibiotics?
Int. J. Mol. Sci. 2017, 18(7), 1344; https://doi.org/10.3390/ijms18071344 - 23 Jun 2017
Cited by 10
Abstract
Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD). The major objective of the management of these patients is the prevention and effective treatment of exacerbations. Patients that have increased sputum production, associated with purulence and worsening shortness [...] Read more.
Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD). The major objective of the management of these patients is the prevention and effective treatment of exacerbations. Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy. It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens. In some patients, systemic corticosteroids are also indicated to improve symptoms. In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence. It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy. Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition. Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations. Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations. There is a need to design long-term studies to evaluate these interventions in the natural history of the disease. The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
Open AccessReview
Inhaled Antibiotic Therapy in Chronic Respiratory Diseases
Int. J. Mol. Sci. 2017, 18(5), 1062; https://doi.org/10.3390/ijms18051062 - 16 May 2017
Cited by 15
Abstract
The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas [...] Read more.
The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
Open AccessReview
Taste Receptors Mediate Sinonasal Immunity and Respiratory Disease
Int. J. Mol. Sci. 2017, 18(2), 437; https://doi.org/10.3390/ijms18020437 - 17 Feb 2017
Cited by 5
Abstract
The bitter taste receptor T2R38 has been shown to play a role in the pathogenesis of chronic rhinosinusitis (CRS), where the receptor functions to enhance upper respiratory innate immunity through a triad of beneficial immune responses. Individuals with a functional version of T2R38 [...] Read more.
The bitter taste receptor T2R38 has been shown to play a role in the pathogenesis of chronic rhinosinusitis (CRS), where the receptor functions to enhance upper respiratory innate immunity through a triad of beneficial immune responses. Individuals with a functional version of T2R38 are tasters for the bitter compound phenylthiocarbamide (PTC) and exhibit an anti-microbial response in the upper airway to certain invading pathogens, while those individuals with a non-functional version of the receptor are PTC non-tasters and lack this beneficial response. The clinical ramifications are significant, with the non-taster genotype being an independent risk factor for CRS requiring surgery, poor quality-of-life (QOL) improvements post-operatively, and decreased rhinologic QOL in patients with cystic fibrosis. Furthermore, indirect evidence suggests that non-tasters also have a larger burden of biofilm formation. This new data may influence the clinical management of patients with infectious conditions affecting the upper respiratory tract and possibly at other mucosal sites throughout the body. Full article
(This article belongs to the Special Issue Lung Diseases: Chronic Respiratory Infections) Printed Edition available
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