Journal of Clinical Medicine

Editorial

4 pages, 210 KiB

Open AccessEditorial

Special Issue: Rare Respiratory Diseases: A Personal and Public Health Issue

by María Magallón, Lucía Bañuls, Silvia Castillo, María Mercedes Navarro-García, Cruz González and Francisco Dasí

J. Clin. Med. 2021, 10(24), 5906; https://doi.org/10.3390/jcm10245906 - 16 Dec 2021

Viewed by 1882

Abstract

In the 1970s, the term “rare disease” was coined to describe a category of inherited metabolic diseases with low prevalence and a wide range of symptoms [...] Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

Research

Jump to: Editorial, Review

13 pages, 845 KiB

Open AccessArticle

Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency

by Mònica Pons, Alexa Núñez, Cristina Esquinas, María Torres-Durán, Juan Luis Rodríguez-Hermosa, Myriam Calle, Ramón Tubio-Pérez, Irene Belmonte, Francisco Rodríguez-Frías, Esther Rodríguez, Joan Genescà, Marc Miravitlles and Miriam Barrecheguren

J. Clin. Med. 2021, 10(8), 1724; https://doi.org/10.3390/jcm10081724 - 16 Apr 2021

Cited by 11 | Viewed by 2143

Abstract

Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. [...] Read more.

Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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8 pages, 996 KiB

Open AccessArticle

Alpha-1 Antitrypsin Screening in a Selected Cohort of Patients Affected by Chronic Pulmonary Diseases in Naples, Italy

by Anna Annunziata, Ilaria Ferrarotti, Antonietta Coppola, Maurizia Lanza, Pasquale Imitazione, Sara Spinelli, Pierpaolo Di Micco and Giuseppe Fiorentino

J. Clin. Med. 2021, 10(8), 1546; https://doi.org/10.3390/jcm10081546 - 7 Apr 2021

Cited by 11 | Viewed by 2114

Abstract

Introduction. Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations [...] Read more.

Introduction. Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations and over ten years’ duration. The purpose of this study was to evaluate the incidence of alpha-1 antitrypsin deficiency in patients with the chronic pulmonary disease after a thorough screening in the city of Naples in southern Italy. Materials and methods. Two hundred patients suffering from respiratory pathology (chronic obstructive pulmonary disease (COPD), emphysema, asthma, or bronchiectasis) were examined and evaluated in our outpatients’ clinic and tested for serum levels of AAT. Patients who had a respiratory disease suspected of AATD and/or serum AAT < 120 mg/dL underwent genetic testing. Genetic screening was performed on samples from 141 patients. Results. A total of 36 patients had an intermediate deficiency of AAT levels. Among them, 8 were PI*MZ, 6 were PI*MS and 22 had rare pathological mutations. Five patients had a severe AATD, all were composite heterozygous with S or Z allele, while the other allele had a rare pathological mutation. Conclusions. The incidence of genetic defects as AATD in the population of patients affected by chronic respiratory disorders is always a matter of discussion because of the frequent interaction between genes and environmental causes. In our series, numerous rare variants and compound heterozygosity have been described. No homozygous patients have been described. The present is one of few studies available on the incidence of rare variants in the geographic area of the city of Naples. So, our results could be considered interesting not only to know the incidence of AATD and its related rare mutations but also to support early diagnosis and treatments for patients with chronic pulmonary disease and frequent exacerbation and to fight the association with environmental causes of pulmonary damages as smoking. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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16 pages, 4778 KiB

Open AccessArticle

New Laboratory Protocol to Determine the Oxidative Stress Profile of Human Nasal Epithelial Cells Using Flow Cytometry

by Ana Reula, Daniel Pellicer, Silvia Castillo, María Magallón, Miguel Armengot, Guadalupe Herrera, José-Enrique O’Connor, Lucía Bañuls, María Mercedes Navarro-García, Amparo Escribano and Francisco Dasí

J. Clin. Med. 2021, 10(6), 1172; https://doi.org/10.3390/jcm10061172 - 11 Mar 2021

Cited by 7 | Viewed by 4383

Abstract

Several studies have shown the importance of oxidative stress (OS) in respiratory disease pathogenesis. It has been reported that the nasal epithelium may act as a surrogate for the bronchial epithelium in several respiratory diseases involving OS. However, the sample yields obtained from [...] Read more.

Several studies have shown the importance of oxidative stress (OS) in respiratory disease pathogenesis. It has been reported that the nasal epithelium may act as a surrogate for the bronchial epithelium in several respiratory diseases involving OS. However, the sample yields obtained from nasal biopsies are modest, limiting the number of parameters that can be determined. Flow cytometry has been widely used to evaluate cellular OS profiles. It has the advantage that analyses can be performed using a small amount of sample. Therefore, we aimed to set up a new method based on flow cytometry to assess the oxidative profile of human nasal epithelial cells which could be used in research on respiratory diseases. Levels of total nitric oxide, superoxide anion, peroxynitrite, and intracellular peroxides were measured. Reduced thiol levels, such as antioxidant-reduced glutathione and oxidative damaged lipids and proteins, were also analysed. The intracellular calcium levels, plasma membrane potential, apoptosis, and percentage of live cells were also studied. Finally, a strategy to evaluate the mitochondrial function, including mitochondrial hydrogen peroxide, superoxide anion, mitochondrial mass, and membrane potential, was set up. Using small amounts of sample and a non-invasive sampling technique, the described method enables the measurement of a comprehensive set of OS parameters in nasal epithelial cells, which could be useful in research on respiratory diseases. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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13 pages, 1127 KiB

Open AccessArticle

Physical Activity and Mental Health of Patients with Pulmonary Hypertension during the COVID-19 Pandemic

by Carolin Leoni Dobler, Britta Krüger, Jana Strahler, Christopher Weyh, Kristina Gebhardt, Khodr Tello, Hossein Ardeschir Ghofrani, Natascha Sommer, Henning Gall, Manuel Jonas Richter and Karsten Krüger

J. Clin. Med. 2020, 9(12), 4023; https://doi.org/10.3390/jcm9124023 - 12 Dec 2020

Cited by 16 | Viewed by 3456

Abstract

The aim of the study was to analyze the effect of personal restrictions on physical activity, mental health, stress experience, resilience, and sleep quality in patients with pulmonary hypertension (PH) during the “lockdown” period of the COVID-19 pandemic. In total, 112 PH patients [...] Read more.

The aim of the study was to analyze the effect of personal restrictions on physical activity, mental health, stress experience, resilience, and sleep quality in patients with pulmonary hypertension (PH) during the “lockdown” period of the COVID-19 pandemic. In total, 112 PH patients and 52 age-matched healthy control subjects completed a questionnaire on the topics of physical activity, mental health, resilience, and sleep quality. PH patients had significantly lower physical activity, mental health, and sleep quality compared to age-matched healthy controls. Physical activity positively correlated with mental health and sleep quality in the PH group. Mental wellbeing and life satisfaction could be predicted by total physical activity, sleep, stress level, and resilience. PH patients appeared as an especially vulnerable group, demanding interventions to promote an active lifestyle and protect mental health in these patients. This could be helpful in counseling on how to carry out physical activity while maintaining infection control. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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8 pages, 569 KiB

Open AccessArticle

Serum Levels of Glutamate-Pyruvate Transaminase, Glutamate-Oxaloacetate Transaminase and Gamma-Glutamyl Transferase in 1494 Patients with Various Genotypes for the Alpha-1 Antitrypsin Gene

by José María Hernández Pérez, Ignacio Blanco, Agustín Jesús Sánchez Medina, Laura Díaz Hernández and José Antonio Pérez Pérez

J. Clin. Med. 2020, 9(12), 3923; https://doi.org/10.3390/jcm9123923 - 3 Dec 2020

Cited by 6 | Viewed by 2585

Abstract

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different [...] Read more.

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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16 pages, 2390 KiB

Open AccessArticle

A Revised Protocol for Culture of Airway Epithelial Cells as a Diagnostic Tool for Primary Ciliary Dyskinesia

by Janice L. Coles, James Thompson, Katie L. Horton, Robert A. Hirst, Paul Griffin, Gwyneth M. Williams, Patricia Goggin, Regan Doherty, Peter M. Lackie, Amanda Harris, Woolf T. Walker, Christopher O’Callaghan, Claire Hogg, Jane S. Lucas, Cornelia Blume and Claire L. Jackson

J. Clin. Med. 2020, 9(11), 3753; https://doi.org/10.3390/jcm9113753 - 21 Nov 2020

Cited by 29 | Viewed by 4300

Abstract

Air–liquid interface (ALI) culture of nasal epithelial cells is a valuable tool in the diagnosis and research of primary ciliary dyskinesia (PCD). Ex vivo samples often display secondary dyskinesia from cell damage during sampling, infection or inflammation confounding PCD diagnostic results. ALI culture [...] Read more.

Air–liquid interface (ALI) culture of nasal epithelial cells is a valuable tool in the diagnosis and research of primary ciliary dyskinesia (PCD). Ex vivo samples often display secondary dyskinesia from cell damage during sampling, infection or inflammation confounding PCD diagnostic results. ALI culture enables regeneration of healthy cilia facilitating differentiation of primary from secondary ciliary dyskinesia. We describe a revised ALI culture method adopted from April 2018 across three collaborating PCD diagnostic sites, including current University Hospital Southampton COVID-19 risk mitigation measures, and present results. Two hundred and forty nasal epithelial cell samples were seeded for ALI culture and 199 (82.9%) were ciliated. Fifty-four of 83 (63.9%) ex vivo samples which were originally equivocal or insufficient provided diagnostic information following in vitro culture. Surplus basal epithelial cells from 181 nasal brushing samples were frozen in liquid nitrogen; 39 samples were ALI-cultured after cryostorage and all ciliated. The ciliary beat patterns of ex vivo samples (by high-speed video microscopy) were recapitulated, scanning electron microscopy demonstrated excellent ciliation, and cilia could be immuno-fluorescently labelled (anti-alpha-tubulin and anti-RSPH4a) in representative cases that were ALI-cultured after cryostorage. In summary, our ALI culture protocol provides high ciliation rates across three centres, minimising patient recall for repeat brushing biopsies and improving diagnostic certainty. Cryostorage of surplus diagnostic samples was successful, facilitating PCD research. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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14 pages, 7135 KiB

Open AccessArticle

Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia

by Noelia Baz-Redón, Sandra Rovira-Amigo, Mónica Fernández-Cancio, Silvia Castillo-Corullón, Maria Cols, M. Araceli Caballero-Rabasco, Óscar Asensio, Carlos Martín de Vicente, Maria del Mar Martínez-Colls, Alba Torrent-Vernetta, Inés de Mir-Messa, Silvia Gartner, Ignacio Iglesias-Serrano, Ana Díez-Izquierdo, Eva Polverino, Esther Amengual-Pieras, Rosanel Amaro-Rodríguez, Montserrat Vendrell, Marta Mumany, María Teresa Pascual-Sánchez, Belén Pérez-Dueñas, Ana Reula, Amparo Escribano, Francisco Dasí, Miguel Armengot-Carceller, Marta Garrido-Pontnou, Núria Camats-Tarruella and Antonio Moreno-Galdó Show full author list Hide full author list

J. Clin. Med. 2020, 9(11), 3603; https://doi.org/10.3390/jcm9113603 - 9 Nov 2020

Cited by 10 | Viewed by 3842

Abstract

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique [...] Read more.

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspicion of PCD. Sixty-eight (91.9%) patients were evaluable for all tested antibodies. Thirty-three cases (44.6%) presented an absence or mislocation of protein in the ciliary axoneme (15 absent and 3 proximal distribution of DNAH5 in the ciliary axoneme, 3 absent DNAH5 and DNALI1, 7 absent DNALI1 and cytoplasmatic localization of GAS8, 1 absent GAS8, 3 absent RSPH9 and 1 absent RSPH4A). Fifteen patients had confirmed or highly likely PCD but normal immunofluorescence results (68.8% sensitivity and 100% specificity). In conclusion, immunofluorescence analysis is a quick, available, low-cost and reliable diagnostic test for PCD, although it cannot be used as a standalone test. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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10 pages, 1075 KiB

Open AccessArticle

Late Diagnosis of Infants with PCD and Neonatal Respiratory Distress

by Myrofora Goutaki, Florian S. Halbeisen, Angelo Barbato, Suzanne Crowley, Amanda Harris, Robert A. Hirst, Bülent Karadag, Vendula Martinu, Lucy Morgan, Christopher O’Callaghan, Ugur Ozçelik, Sergio Scigliano, Santiago Ucros, Panayiotis Yiallouros, Sven M. Schulzke and Claudia E. Kuehni

J. Clin. Med. 2020, 9(9), 2871; https://doi.org/10.3390/jcm9092871 - 4 Sep 2020

Cited by 20 | Viewed by 3557

Abstract

Neonatal respiratory distress (NRD) is common among infants with primary ciliary dyskinesia (PCD), but we do not know whether affected neonates receive a timely diagnosis. We used data from the international PCD cohort and assessed the proportion of patients with PCD who had [...] Read more.

Neonatal respiratory distress (NRD) is common among infants with primary ciliary dyskinesia (PCD), but we do not know whether affected neonates receive a timely diagnosis. We used data from the international PCD cohort and assessed the proportion of patients with PCD who had a history of NRD and their age at diagnosis, stratifying by presence of laterality defects. First we analyzed data from all participants diagnosed after 2000, followed by individuals from a subgroup diagnosed using stricter criteria. Among the 1375 patients in the study, 45% had a history of NRD and 42% had laterality defects. Out of the 476 children with definite PCD diagnosis, 55% had a history of NRD and 50% had laterality defects. Overall, 30% of children with PCD were diagnosed during the first 12 months of life. This varied from 13% in those with situs solitus and no NRD, to 21% in those with situs solitus and NRD, 33% in those with situs anomalies but no NRD, and 52% in those with both situs anomalies and NRD. Our results suggest that we need to improve our knowledge of the neonatal presentation of infants with PCD and apply it so that these patients will receive appropriate care sooner. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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11 pages, 1982 KiB

Open AccessArticle

MiRNA Expression Profile in the Airways Is Altered during Pulmonary Exacerbation in Children with Cystic Fibrosis—A Preliminary Report

by Zuzanna Stachowiak, Irena Wojsyk-Banaszak, Katarzyna Jończyk-Potoczna, Beata Narożna, Wojciech Langwiński, Zdzisława Kycler, Paulina Sobkowiak, Anna Bręborowicz and Aleksandra Szczepankiewicz

J. Clin. Med. 2020, 9(6), 1887; https://doi.org/10.3390/jcm9061887 - 16 Jun 2020

Cited by 13 | Viewed by 2378

Abstract

MicroRNAs are small non-coding RNAs that regulate immune response and inflammation. We assumed that miRNAs may be involved in the immune response during cystic fibrosis pulmonary exacerbations (CFPE) and that altered expression profile in the airways and blood may underlie clinical outcomes in [...] Read more.

MicroRNAs are small non-coding RNAs that regulate immune response and inflammation. We assumed that miRNAs may be involved in the immune response during cystic fibrosis pulmonary exacerbations (CFPE) and that altered expression profile in the airways and blood may underlie clinical outcomes in CF pediatric patients. Methods: We included 30 pediatric patients diagnosed with cystic fibrosis. The biologic material (blood, sputum, exhaled breath condensate) was collected during pulmonary exacerbation and in stable condition. The miRNA expression profile from blood and sputum (n = 6) was done using the next-generation sequencing. For validation, selected four miRNAs were analyzed by qPCR in exosomes from sputum supernatant and exhaled breath condensate (n = 24). NGS analysis was done in Base Space, correlations of gene expression with clinical data were done in Statistica. Results: The miRNA profiling showed that four miRNAs (miR-223, miR-451a, miR-27b-3p, miR-486-5p) were significantly altered during pulmonary exacerbation in CF patients in sputum but did not differ significantly in blood. MiRNA differently expressed in exhaled breath condensate (EBC) and sputum showed correlation with clinical parameters in CFPE. Conclusion: MiRNA expression profile changes in the airways during pulmonary exacerbation in CF pediatric patients. We suggest that miRNA alterations during CFPE are restricted to the airways and strongly correlate with clinical outcome. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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15 pages, 1718 KiB

Open AccessArticle

Long-Term Treatment Outcome of Progressive Mycobacterium avium Complex Pulmonary Disease

by Kiyoharu Fukushima, Seigo Kitada, Yuko Abe, Yuji Yamamoto, Takanori Matsuki, Hiroyuki Kagawa, Yohei Oshitani, Kazuyuki Tsujino, Kenji Yoshimura, Mari Miki, Keisuke Miki and Hiroshi Kida

J. Clin. Med. 2020, 9(5), 1315; https://doi.org/10.3390/jcm9051315 - 2 May 2020

Cited by 19 | Viewed by 3876

Abstract

Background: Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly understood. Methods: We retrospectively evaluated the clinical characteristics and long-term outcomes in [...] Read more.

Background: Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly understood. Methods: We retrospectively evaluated the clinical characteristics and long-term outcomes in patients with chemo-naïve progressive MAC-PD, hospitalized for first-line multidrug therapy. Results: Among 125 patients, 86 (68.8%) received standardized treatment (rifampicin, ethambutol, clarithromycin), 25 (20.0%) received a fluoroquinolone (FQ)-containing regimen, and 53 (42.4%) received aminoglycoside injection. The sputum conversion rate was 80.0%, and was independently associated with standardized treatment. The incidence of refractory disease (45.6%) was independently and negatively associated with standardized regimen and aminoglycoside use. Choice of an FQ-containing regimen was not associated with positive outcome. Clarithromycin resistance occurred in 16.8% and was independently associated with refractory disease. MAC-PD-associated death occurred in 3.3% of patients with non-cavitary nodular bronchiectasis (NB) and 21.3% with cavitary MAC-PD over a median follow-up period of 56.4 months. The rates of MAC-PD-associated death were comparable between cavitary-NB and fibrocavitary disease. Concurrent chronic pulmonary aspergillosis (CPA) occurred in 13 (17.3%) patients with cavitary MAC-PD, and age, diabetes mellitus, and CPA were independent risk factors for mortality. Conclusions: Standardized intensive multidrug treatment reduces disease progression and persistence in progressive MAC-PD. Cavitary NB may differ from, rather than being just an advanced stage of, non-cavitary NB. The high incidence and significant mortality of CPA in cavitary MAC-PD highlight the need for early diagnosis and treatment. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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10 pages, 581 KiB

Open AccessArticle

Knowledge of Rare Respiratory Diseases among Paediatricians and Medical School Students

by María Ángeles Requena-Fernández, Francisco Dasí, Silvia Castillo, Rafael Barajas-Cenobi, María Mercedes Navarro-García and Amparo Escribano

J. Clin. Med. 2020, 9(3), 869; https://doi.org/10.3390/jcm9030869 - 22 Mar 2020

Cited by 7 | Viewed by 2954

Abstract

Alpha-1-antitrypsin deficiency (AATD) and primary ciliary dyskinesia (PCD) are underdiagnosed rare diseases showing a median diagnostic delay of five to ten years, which has negative effects on patient prognosis. Lack of awareness and education among healthcare professionals involved in the management of these [...] Read more.

Alpha-1-antitrypsin deficiency (AATD) and primary ciliary dyskinesia (PCD) are underdiagnosed rare diseases showing a median diagnostic delay of five to ten years, which has negative effects on patient prognosis. Lack of awareness and education among healthcare professionals involved in the management of these patients have been suggested as possible causes. Our aim was to assess knowledge of these diseases among paediatricians and medical school students to determine which knowledge areas are most deficient. A survey was designed with questions testing fundamental aspects of the diagnosis and treatment of AATD and PCD. A score equal to or greater than 50% of the maximum score was set as the level necessary to ensure a good knowledge of both diseases. Our results indicate a profound lack of knowledge of rare respiratory diseases among paediatric professionals and medical students, suggesting that it is necessary to increase rare respiratory diseases training among all physicians responsible for suspecting and diagnosing them; this will allow early diagnosis and the setup of preventive measures and appropriate early-stage treatment. The first step in closing this knowledge gap could be to include relevant material in the medical syllabus. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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12 pages, 942 KiB

Open AccessArticle

Understanding Primary Ciliary Dyskinesia: Experience From a Mediterranean Diagnostic Reference Centre

by Miguel Armengot-Carceller, Ana Reula, Manuel Mata-Roig, Jordi Pérez-Panadés, Lara Milian-Medina and Carmen Carda-Batalla

J. Clin. Med. 2020, 9(3), 810; https://doi.org/10.3390/jcm9030810 - 16 Mar 2020

Cited by 4 | Viewed by 2429

Abstract

Background: Due to the lack of a gold standard diagnostic test, reference centres with experienced personnel and costly procedures are needed for primary ciliary dyskinesia (PCD) diagnostics. Diagnostic flowcharts always start with clinical symptoms. Therefore, the aim of this work is to define [...] Read more.

Background: Due to the lack of a gold standard diagnostic test, reference centres with experienced personnel and costly procedures are needed for primary ciliary dyskinesia (PCD) diagnostics. Diagnostic flowcharts always start with clinical symptoms. Therefore, the aim of this work is to define differential clinical criteria so that only patients clinically compatible with PCD are referred to reference centres. Materials and methods: 18 variables from 476 Mediterranean patients with clinically suspicious PCD were collected. After analysing cilia function and ultrastructure, 89 individuals were diagnosed with PCD and 387 had a negative diagnosis. Simple logistic regression analysis, considering PCD as a dependent variable and the others as independent variables, was done. In order to define the variables that best explain PCD, a step-wise logistic regression model was defined. Aiming to classify individuals as PCD or PCD-like patients, based on variables included in the study, a classification and regression tree (CART) was designed. Results and conclusions: Simple logistic regression analysis shows statistically significant association between age at the beginning of their symptomatology, periodicity, fertility, situs inversus, recurrent otitis, atelectasis, bronchiectasis, chronic productive cough, rhinorrea, rhinusinusitis and recurrent pneumonias, and PCD. The step-wise logistic regression model selected situs inversus, atelectasis, rhinorrea, chronic productive cough, bronchiectasis, recurrent pneumonias, and otitis as PCD predictive variables (82% sensitivity, 88% specificity, and 0.92 Area Under the Curve (AUC)). A decision tree was designed in order to classify new individuals based on pansinusitis, situs inversus, periodicity, rhinorrea, bronchiectasis, and chronic wet cough. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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Review

Jump to: Editorial, Research

25 pages, 1650 KiB

Open AccessReview

Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases

by María Magallón, Sara Pastor, Ana Esther Carrión, Lucía Bañuls, Daniel Pellicer, Silvia Castillo, Sergio Bondía, María Mercedes Navarro-García, Cruz González and Francisco Dasí

J. Clin. Med. 2021, 10(6), 1268; https://doi.org/10.3390/jcm10061268 - 18 Mar 2021

Cited by 15 | Viewed by 3798 | Correction

Abstract

Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the [...] Read more.

Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the use of antioxidants as therapeutic agents to minimize the effects of OS are discussed in this review. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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29 pages, 2523 KiB

Open AccessReview

Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?

by Lucía Bañuls, Daniel Pellicer, Silvia Castillo, María Mercedes Navarro-García, María Magallón, Cruz González and Francisco Dasí

J. Clin. Med. 2020, 9(8), 2577; https://doi.org/10.3390/jcm9082577 - 8 Aug 2020

Cited by 16 | Viewed by 6481

Abstract

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way [...] Read more.

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical trials targeting CF and AATD, especially using adeno-associated viral vectors, resulting in a good safety profile but with low efficacy in protein expression. Other strategies, such as non-viral vectors and more recently gene editing tools, have also been used to address these diseases in pre-clinical studies. The first gene therapy approach in PCD was in 2009 when a lentiviral transduction was performed to restore gene expression in vitro; since then, transcription activator-like effector nucleases (TALEN) technology has also been applied in primary cell culture. Gene therapy is an encouraging alternative treatment for these respiratory diseases; however, more research is needed to ensure treatment safety and efficacy. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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19 pages, 1978 KiB

Open AccessReview

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy

by José Luis López-Campos, Laura Carrasco Hernandez and Candelaria Caballero Eraso

J. Clin. Med. 2020, 9(8), 2526; https://doi.org/10.3390/jcm9082526 - 5 Aug 2020

Cited by 11 | Viewed by 4048

Abstract

Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. [...] Read more.

Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field. Full article

(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)

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