Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study.

Lancet Respir Med. 2016 Dec 20;:

Authors: Konstan MW, McKone EF, Moss RB, Marigowda G, Tian S, Waltz D, Huang X, Lubarsky B, Rubin J, Millar SJ, Pasta DJ, Mayer-Hamblett N, Goss CH, Morgan W, Sawicki GS

Abstract
BACKGROUND: The 24-week safety and efficacy of lumacaftor/ivacaftor combination therapy was shown in two randomised controlled trials (RCTs)-TRAFFIC and TRANSPORT-in patients with cystic fibrosis who were aged 12 years or older and homozygous for the F508del-CFTR mutation. We aimed to assess the long-term safety and efficacy of extended lumacaftor/ivacaftor therapy in this group of patients in PROGRESS, the long-term extension of TRAFFIC and TRANSPORT.
METHODS: PROGRESS was a phase 3, parallel-group, multicentre, 96-week study of patients who completed TRAFFIC or TRANSPORT in 191 sites in 15 countries. Patients were eligible if they were at least 12 years old with cystic fibrosis and homozygous for the F508del-CFTR mutation. Exclusion criteria included any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering the study drug to the participant, history of drug intolerance, and history of poor compliance with the study drug. Patients who previously received active treatment in TRANSPORT or TRAFFIC remained on the same dose in PROGRESS. Patients who had received placebo in TRANSPORT or TRAFFIC were randomly assigned (1:1) to receive lumacaftor (400 mg every 12 h)/ivacaftor (250 mg every 12 h) or lumacaftor (600 mg once daily)/ivacaftor (250 mg every 12 h). The primary outcome was to assess the long-term safety of combined therapy. The estimated annual rate of decline in percent predicted FEV1 (ppFEV1) in treated patients was compared with that of a matched registry cohort. Efficacy analyses were based on modified intention-to-treat, such that data were included for all patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01931839.
FINDINGS: Between Oct 24, 2013, and April 7, 2016, 1030 patients from the TRANSPORT and TRAFFIC studies enrolled in PROGRESS, and 1029 received at least one dose of study drug. 340 patients continued treatment with lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h; 176 patients who had received placebo in the TRANSPORT or TRAFFIC studies initiated treatment with lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h, the commercially available dose, for which data are presented. The most common adverse events were infective pulmonary exacerbations, cough, increased sputum, and haemoptysis. Modest blood pressure increases seen in TRAFFIC and TRANSPORT were also observed in PROGRESS. For patients continuing treatment, the mean change from baseline in ppFEV1 was 0·5 (95% CI -0·4 to 1·5) at extension week 72 and 0·5 (-0·7 to 1·6) at extension week 96; change in BMI was 0·69 (0·56 to 0·81) at extension week 72 and 0·96 (0·81 to 1·11) at extension week 96. The annualised pulmonary exacerbation rate in patients continuing treatment through extension week 96 (0·65, 0·56 to 0·75) remained lower than the placebo rate in TRAFFIC and TRANSPORT. The annualised rate of ppFEV1 decline was reduced in lumacaftor/ivacaftor-treated patients compared with matched controls (-1·33, -1·80 to -0·85 vs -2·29, -2·56 to -2·03). The efficacy and safety profile of the lumacaftor 600 mg once daily/ivacaftor 250 mg every 12 h groups was generally similar to that of the lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h groups.
INTERPRETATION: The long-term safety profile of lumacaftor/ivacaftor combination therapy was consistent with previous RCTs. Benefits continued to be observed with longer-term treatment, and lumacaftor/ivacaftor was associated with a 42% slower rate of ppFEV1 decline than in matched registry controls.
FUNDING: Vertex Pharmaceuticals Incorporated.

PMID: 28011037 [PubMed - as supplied by publisher]

A little CFTR can change a lot: slowing cystic fibrosis progression.

Lancet Respir Med. 2016 Dec 20;:

Authors: Rowe SM

PMID: 28011036 [PubMed - as supplied by publisher]

The functional mechanisms and clinical application of read-through drugs.

Yi Chuan. 2016 Jul 20;38(7):623-633

Authors: Yang F, Zaiyue S, Mingmin G

Abstract
According to previous reports, nearly one in 10 genetic diseases are caused by nonsense mutations around the world. Nonsense mutations lead to premature transcription terminations in cells, which in turn generate non-functional, truncated proteins. In recent years, read-through drugs are playing increasing prominent roles in the researches related to genetic diseases caused by nonsense mutations. However, due to the fact that the mechanisms lying behind translation termination still remain to be elucidated, the mechanistic research and clinical application of read-through drugs are facing new challenges. This review mainly discusses about the pathogenesis of genetic diseases caused by nonsense mutations, and then introduces the current clinical application of read-through drugs. Finally, we display some problems that remain to be solved and propose some possible coping strategies.

PMID: 27733335 [PubMed - indexed for MEDLINE]

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"cystic fibrosis"

These pubmed results were generated on 2016/12/23

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"cystic fibrosis"

These pubmed results were generated on 2016/12/22

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The Coupling of Peripheral Blood Pressure and Ventilatory Responses during Exercise in Young Adults with Cystic Fibrosis.

PLoS One. 2016;11(12):e0168490

Authors: Van Iterson EH, Wheatley CM, Baker SE, Olson TP, Morgan WJ, Snyder EM

Abstract
PURPOSE: Cystic fibrosis (CF) is commonly recognized as a pulmonary disease associated with reduced airway function. Another primary symptom of CF is low exercise capacity where ventilation and gas-exchange are exacerbated. However, an independent link between pathophysiology of the pulmonary system and abnormal ventilatory and gas-exchange responses during cardiopulmonary exercise testing (CPET) has not been established in CF. Complicating this understanding, accumulating evidence suggests CF demonstrate abnormal peripheral vascular function; although, the clinical implications are unclear. We hypothesized that compared to controls, relative to total work performed (WorkTOT), CF would demonstrate increased ventilation accompanied by augmented systolic blood pressure (SBP) during CPET.
METHODS: 16 CF and 23 controls (age: 23±4 vs. 27±4 years, P = 0.11; FEV1%predicted: 73±14 vs. 96±5, P<0.01) participated in CPET. Breath-by-breath oxygen uptake ([Formula: see text]), ventilation ([Formula: see text]), and carbon dioxide output ([Formula: see text]) were measured continuously during incremental 3-min stage step-wise cycle ergometry CPET. SBP was measured via manual sphygmomanometry. Linear regression was used to calculate [Formula: see text] slope from rest to peak-exercise.
RESULTS: Compared to controls, CF performed less WorkTOT during CPET (90±19 vs. 43±14 kJ, respectively, P<0.01). With WorkTOT as a covariate, peak [Formula: see text] (62±8 vs. 90±4 L/min, P = 0.76), [Formula: see text] (1.8±0.3 vs. 2.7±0.1 L/min, P = 0.40), and SBP (144±13 vs. 152±6 mmHg, P = 0.88) were similar between CF and controls, respectively; whereas CF demonstrated increased [Formula: see text] slope (38±4 vs. 28±2, P = 0.02) but lower peak [Formula: see text] versus controls (22±5 vs. 33±4 mL/kg/min, P<0.01). There were modest-to-moderate correlations between peak SBP with [Formula: see text] (r = 0.30), [Formula: see text] (r = 0.70), and [Formula: see text] (r = 0.62) in CF.
CONCLUSIONS: These data suggest that relative to WorkTOT, young adults with mild-to-moderate severity CF demonstrate augmented [Formula: see text] slope accompanied by increased SBP during CPET. Although the underlying mechanisms remain unclear, the coupling of ventilatory inefficiency with increased blood pressure suggest important contributions from peripheral pathophysiology to low exercise capacity in CF.

PMID: 27997623 [PubMed - in process]

Intracellular Chloride Concentration Changes Modulate IL-1β Expression and Secretion in Human Bronchial Epithelial Cultured Cells.

J Cell Biochem. 2016 Dec 20;:

Authors: Clauzure M, Valdivieso ÁG, Massip-Copiz MM, Mori C, Dugour AV, Figueroa JM, Coloma TA

Abstract
Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which encodes a cAMP-regulated chloride channel. Several cellular functions are altered in CF cells. However, it is not clear how the CFTR failure induces those alterations. We have found previously several genes differentially expressed in CF cells, including c-Src, MUC1, MTND4 and CISD1 (CFTR-dependent genes). Recently, we also reported the existence of several chloride-dependent genes, among them GLRX5 and RPS27. Here, varying the intracellular chloride concentration [Cl(-) ]i of IB3-1 CF bronchial epithelial cells, we show that IL-1β mRNA expression and secretion are also under Cl(-) modulation. The response to Cl(-) is biphasic, with maximal effects at 75 mM Cl(-) . The regulation of the IL-1β mRNA expression involves an IL-1β autocrine effect, since in the presence of the IL-1β receptor antagonist IL1RN or anti-IL-1β blocking antibody, the mRNA response to Cl(-) disappeared. Similar effects were obtained with the JNK inhibitor SP600125, the c-Src inhibitor PP2 and the IKK inhibitor III (BMS-345541). On the other hand, the IL-1β secretion is still modulated by Cl(-) in the presence of IL-1RN, IL-1β blocking antibody or cycloheximide, suggesting that Cl(-) is affecting the IL-1β maturation/secretion, which in turn starts an autocrine positive feedback loop. In conclusion, the Cl(-) anion acts as a second messenger for CFTR, modulating the IL-1β maturation/secretion. The results also imply that, depending on its intracellular concentration, Cl(-) could be a pro-inflammatory mediator. This article is protected by copyright. All rights reserved.

PMID: 27996167 [PubMed - as supplied by publisher]

Gene therapy for haemophilia.

Cochrane Database Syst Rev. 2016 Dec 20;12:CD010822

Authors: Sharma A, Easow Mathew M, Sriganesh V, Reiss UM

Abstract
BACKGROUND: Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review.
OBJECTIVES: To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016.
SELECTION CRITERIA: Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX.
DATA COLLECTION AND ANALYSIS: No trials of gene therapy for haemophilia were found.
MAIN RESULTS: No trials of gene therapy for haemophilia were identified.
AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

PMID: 27996087 [PubMed - as supplied by publisher]

Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis.

Sci Rep. 2016 Dec 20;6:38776

Authors: Celestino-Soper PB, Simpson E, Tumbleson Brink D, Lynnes TC, Dlouhy S, Vatta M, Yeley J, Brown C, Bai S

Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by the accumulation of sticky and heavy mucus that can damage several organs. CF shows variable expressivity in affected individuals, but it typically causes respiratory and digestive complications as well as congenital bilateral absence of the vas deferens in males. Individuals with classic CF usually have variants that produce a defective protein from both alleles of the CFTR gene. Individuals with other variants may present with classic, non-classic, or milder forms of CF due to lower levels of functional CFTR protein. This article reports the genetic analysis of a female with features of asthma and mild or non-classic CF. CFTR sequencing demonstrated that she is a carrier for a maternally derived 5T/12TG variant. Deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA) showed the presence of an intragenic paternally derived duplication involving exons 7-11 of the CFTR gene. This duplication is predicted to result in the production of a truncated CFTR protein lacking the terminal part of the nucleotide-binding domain 1 (NBD1) and thus is likely to be a non-functioning allele. The combination of this large intragenic duplication and 5T/12TG is the probable cause of the mild or non-classic CF features in this individual.

PMID: 27996019 [PubMed - in process]

Ralstonia mannitolilytica in cystic fibrosis: A new predictor of worse outcomes.

Respir Med Case Rep. 2017;20:48-50

Authors: Coman I, Bilodeau L, Lavoie A, Carricart M, Tremblay F, Zlosnik JE, Berthiaume Y

Abstract
BACKGROUND: Patients with Cystic Fibrosis are subject to repeated respiratory tract infections, with recent increasing isolation of unusual pathogens. Ralstonia species have lately been isolated at our institution, an organism historically frequently misidentified as Burkholderia or Pseudomonas. The prevalence of Ralstonia spp. in cystic fibrosis populations has yet to be determined, along with its clinical implications.
CASE PRESENTATIONS: Seven patients out of the 301 followed at our cystic fibrosis clinic have had Ralstonia strains identified in their respiratory tract. Most strains identified were multi-drug resistant. After aquisition of Ralstonia spp., the patients' clinical course was characterized by more frequent and more severe respiratory infections along with prolonged hospitalizations, greater decline of lung function, and greater mortality. The mortality rate in this group of patients was 86%. No other factor that could explain such a dramatic evolution was identified upon review of patient data. Some of the strains involved were recognized as clones on Pulse Field Electrophoresis Gel, raising the question of person-to-person transmission.
CONCLUSION: New pathogens are identified with the evolution of the microbiota in cystic fibrosis respiratory tracts. In our cohort of patients, acquisition of Ralstonia spp. was associated with dramatic outcomes in terms of disease acceleration and raised mortality rates. It is of critical importance to continue to better define the prevalence and clinical impact of Ralstonia in cystic fibrosis populations.

PMID: 27995056 [PubMed]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

Cystic Fibrosis

These pubmed results were generated on 2016/12/21

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

Cystic Fibrosis

These pubmed results were generated on 2016/12/20

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Sinonasal characteristics and quality of life by SNOT-22 in adult patients with cystic fibrosis.

Eur Arch Otorhinolaryngol. 2016 Dec 18;

Authors: Kang SH, Meotti CD, Bombardelli K, Piltcher OB, de Tarso Roth Dalcin P

Abstract
The prevalence of chronic sinus disease in cystic fibrosis (CF) has gradually increased. Sinonasal involvement may have influence on pulmonary exacerbations and can have a negative impact on the quality of life. To evaluate nasal characteristics and quality of life in adult patients with CF; to establish an association and determine the predictors in SNOT-22 questionnaire. Cross- sectional study with prospective data collection was performed to evaluate adult CF patients. Patients underwent clinical evaluation, lung function tests, nasal endoscopy, and paranasal sinuses CT scan. All the patients answered the SNOT-22 questionnaire.
RESULTS: A total of 91 patients were allocated, of which, 45.1% were male. Patients were divided into three groups by SNOT-22. A high average age, late age of diagnosis, rhinitis symptoms, and clinical criteria for rhinosinusitis were observed more frequently in patients with high SNOT-22 scores (p < 0.05). Overall, 84.6% patients had abnormal CT findings, with aplasia/hypoplasia of the sphenoid sinus being the most common finding. In multiple regression model, age, female gender, and Pseudomonas aeruginosa in the sputum were associated with high SNOT-22 scores in the nasal domain. Hyposmia and lack of medial bulging of lateral nasal wall were variables associated with high SNOT-22 scores in the quality of life domain. In total score, there was a positive association with age and the presence of P. aeruginosa in sputum. Despite high prevalence of abnormal tomographic findings, patients reported mild intensity of sinonasal symptoms. Advanced age and the presence of P. aeruginosa were associated with higher SNOT-22 scores.

PMID: 27990603 [PubMed - as supplied by publisher]

The Development of Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) During Gastric Repair Is Absent in the Aged Stomach.

Cell Mol Gastroenterol Hepatol. 2016 Sep;2(5):605-624

Authors: Engevik AC, Feng R, Choi E, White S, Bertaux-Skeirik N, Li J, Mahe MM, Aihara E, Yang L, DiPasquale B, Oh S, Engevik KA, Giraud AS, Montrose MH, Medvedovic M, Helmrath MA, Goldenring JR, Zavros Y

Abstract
BACKGROUND & AIMS: During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2-expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration.
METHODS: Acetic acid ulcers were induced in young (2-3 mo) and aged (18-24 mo) C57BL/6 mice to determine the quality of ulcer repair with advancing age. Yellow chameleon 3.0 mice were used to generate yellow fluorescent protein-expressing organoids for transplantation. Yellow fluorescent protein-positive gastric organoids were transplanted into the submucosa and lumen of the stomach immediately after ulcer induction. Gastric tissue was collected and analyzed to determine the engraftment of organoid-derived cells within the regenerating epithelium.
RESULTS: Wound healing in young mice coincided with the emergence of SPEM within the ulcerated region, a response that was absent in the aged stomach. Although aged mice showed less metaplasia surrounding the ulcerated tissue, organoid-transplanted aged mice showed regenerated gastric glands containing organoid-derived cells. Organoid transplantation in the aged mice led to the emergence of SPEM and gastric regeneration.
CONCLUSIONS: These data show the development of SPEM during gastric repair in response to injury that is absent in the aged stomach. In addition, gastric organoids in an injury/transplantation mouse model promoted gastric regeneration.

PMID: 27990460 [PubMed - in process]

Pharmaceutical Approval Update.

P T. 2016 Dec;41(12):748-750

Authors: Kaufman MB

Abstract
Lisinopril oral solution (Qbrelis) for the treatment of hypertension, heart failure, and acute myocardial infarction; etanercept-szzs (Erelzi) for multiple autoimmune disorders; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis.

PMID: 27990075 [PubMed - in process]

Differences between WHO AND CDC early growth measurements in the assessment of Cystic Fibrosis clinical outcomes.

J Cyst Fibros. 2016 Dec 15;:

Authors: Usatin D, Yen EH, McDonald C, Asfour F, Pohl J, Robson J

Abstract
BACKGROUND: Early childhood growth status has been used to predict long-term clinical outcomes in Cystic Fibrosis (CF) patients. Adulthood CF outcomes based on early weight-for-length (WFL) measurements, using either World Health Organization (WHO) or Centers for Disease Control (CDC) scales, have not been compared.
METHODS: Cystic Fibrosis Foundation registry patients were studied (n=3014). Participants were categorized at age two years as WFL <50th percentile on both WHO and CDC scales, ≥50th percentile on WHO but not CDC, or ≥50th percentile on both. Pulmonary function and overall survival were assessed at age 18years.
RESULTS: Stepwise gains in pulmonary function and lung transplant-free survival were noted across the three increasing WFL categories.
CONCLUSIONS: Children with CF who achieve higher WFL at age two years have improved pulmonary and survival outcomes into adulthood. CF providers should continue to utilize current early growth recommendations, with goal WFL ≥50th percentile on CDC growth charts before age two.

PMID: 27989470 [PubMed - as supplied by publisher]

Increasing sputum levels of gamma-glutamyltransferase may identify cystic fibrosis patients who do not benefit from inhaled glutathione.

J Cyst Fibros. 2016 Dec 14;:

Authors: Corti A, Griese M, Hector A, Pompella A

Abstract
Glutathione (GSH) is decreased in cystic fibrosis (CF) airways, thus its resupply by inhalation has been employed to restore antioxidant defense. CF airways present however increased activity of gamma-glutamyltransferase (GGT), the enzyme specifically capable of degrading GSH, and thus inhaled GSH might be promptly catabolized. In addition, prooxidant reactions are known to originate during GGT-mediated GSH catabolism. We determined levels of GGT in the sputum samples obtained from a previously published trial of GSH inhalation treatment, and analyzed their correlations with inflammatory markers and FEV1% values. Results indicate that differentiating patients with increasing vs. decreasing GGT activity - as measured in sputum before and after the six months duration of the study - may discriminate subjects more likely profiting from inhaled GSH, as opposed to those with increasing GGT in which these treatments might even produce aggravation of the damage.

PMID: 27988297 [PubMed - as supplied by publisher]

Using dendritic cells to evaluate how Burkholderia cenocepacia clonal isolates from a chronically infected cystic fibrosis patient subvert immune functions.

Med Microbiol Immunol. 2016 Dec 16;

Authors: Guadalupe Cabral M, Pereira M, Silva Z, Iria I, Coutinho C, Lopes A, Sá-Correia I, Videira PA

Abstract
Infection with Burkholderia cepacia complex (Bcc) bacteria is a threat to cystic fibrosis (CF) patients, commonly leading to a fatal pneumonia, the cepacia syndrome. It causes a massive production of pro-inflammatory cytokines and leucocyte recruitment to airway epithelium without resolving infection and contributing to tissue lesion. To dissect how Bcc bacteria subvert the immune response, we developed a co-culture model with human dendritic cells (DCs) and B. cenocepacia clonal variants isolated from a chronically infected CF patient, who died with cepacia syndrome. We demonstrated that the two late variants were sevenfold and 17-fold (respectively) more internalized by DCs than the variant that initiated infection. The late variants showed improved survival within DCs (60.29 and 52.82 CFU/DC) compared to the initial variant (0.38 CFU/DC). All clonal isolates induced high expression of inflammatory cytokines IL-8, IL-6, IL-1β, IL-12, IL-23, TNF-α and IL-1β. This pro-inflammatory trait was significantly more pronounced in DCs infected with the late variants than in DCs infected with the variant that initiated patient's infection. All infected DCs failed to upregulate maturation markers, HLA-DR, CD80, CD86 and CD83. Nevertheless, these infected DCs activated approximately twice more T cells than non-infected DCs. Similar T cell activation was observable with respective conditioned media, suggesting a non-antigen-specific activation. Our data indicate that during prolonged infection, B. cenocepacia acquires ability to survive intracellularly, inducing inflammation, while refraining DC's maturation and stimulating non-antigen-specific T cell responses. The co-culture model here developed may be broadly applied to study B. cenocepacia-induced immunomodulation.

PMID: 27987042 [PubMed - as supplied by publisher]

Medical diagnostics for indoor mold exposure.

Int J Hyg Environ Health. 2016 Dec 05;:

Authors: Hurraß J, Heinzow B, Aurbach U, Bergmann KC, Bufe A, Buzina W, Cornely OA, Engelhart S, Fischer G, Gabrio T, Heinz W, Herr CE, Kleine-Tebbe J, Klimek L, Köberle M, Lichtnecker H, Lob-Corzilius T, Merget R, Mülleneisen N, Nowak D, Rabe U, Raulf M, Seidl HP, Steiß JO, Szewszyk R, Thomas P, Valtanen K, Wiesmüller GA

Abstract
In April 2016, the German Society of Hygiene, Environmental Medicine and Preventative Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin (GHUP)) together with other scientific medical societies, German and Austrian medical societies, physician unions and experts has provided an AWMF (Association of the Scientific Medical Societies) guideline 'Medical diagnostics for indoor mold exposure'. This guideline shall help physicians to advise and treat patients exposed indoors to mold. Indoor mold growth is a potential health risk, even without a quantitative and/or causal association between the occurrence of individual mold species and health effects. Apart from the allergic bronchopulmonary aspergillosis (ABPA) and the mycoses caused by mold, there is only sufficient evidence for the following associations between moisture/mold damages and different health effects: Allergic respiratory diseases, asthma (manifestation, progression, exacerbation), allergic rhinitis, exogenous allergic alveolitis and respiratory tract infections/bronchitis. In comparison to other environmental allergens, the sensitizing potential of molds is estimated to be low. Recent studies show a prevalence of sensitization of 3-10% in the total population of Europe. The evidence for associations to mucous membrane irritation and atopic eczema (manifestation, progression, exacerbation) is classified as limited or suspected. Inadequate or insufficient evidence for an association is given for COPD, acute idiopathic pulmonary hemorrhage in children, rheumatism/arthritis, sarcoidosis, and cancer. The risk of infections from indoor molds is low for healthy individuals. Only molds that are capable to form toxins can cause intoxications. The environmental and growth conditions and especially the substrate determine whether toxin formation occurs, but indoor air concentrations are always very low. In the case of indoor moisture/mold damages, everyone can be affected by odor effects and/or impairment of well-being. Predisposing factors for odor effects can be given by genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for impairment of well-being are environmental concerns, anxieties, conditioning and attributions as well as a variety of diseases. Risk groups that must be protected are patients with immunosuppression and with mucoviscidosis (cystic fibrosis) with regard to infections and individuals with mucoviscidosis and asthma with regard to allergies. If an association between mold exposure and health effects is suspected, the medical diagnosis includes medical history, physical examination, conventional allergy diagnosis, and if indicated, provocation tests. For the treatment of mold infections, it is referred to the AWMF guidelines for diagnosis and treatment of invasive Aspergillus infections. Regarding mycotoxins, there are currently no validated test methods that could be used in clinical diagnostics. From the perspective of preventive medicine, it is important that mold damages cannot be tolerated in indoor environments.

PMID: 27986496 [PubMed - as supplied by publisher]

Current strategies for the long-term assessment, monitoring, and management of cystic fibrosis patients treated with CFTR modulator therapy.

J Cyst Fibros. 2016 Dec 13;:

Authors: Elborn JS, Davies J, Mall MA, Flume PA, Plant B

Abstract
The content for this activity is based on the satellite symposium, "Current Strategies for the Long-term Assessment, Monitoring, and Management for Cystic Fibrosis Patients Treated with CFTR Modulator Therapy" that was presented at the 39th European Cystic Fibrosis Society Conference on June 10, 2016 (Online access: http://courses.elseviercme.com/ecfs2016e/619e). The emergence of novel targeted agents, that directly correct CFTR loss function alleles, has created new treatment opportunities for patients with cystic fibrosis with advanced disease. Knowledge of the role of these agents in the clinical setting is quickly evolving and will require physicians to stay acquainted with the latest data as well as evidence-based treatment guidelines in order to achieve optimized cystic fibrosis patient care. Ideally, after diagnosis, a personalized approach would be adapted and tailored to the patient through genome-informed medicine. However, due to the relative recentness of genomic-based therapeutics, physicians may have a limited knowledge base regarding these new treatment options and how to best incorporate these agents into patient management plans. Although cystic fibrosis is still largely regarded as a pediatric disease, the median survival for patients is 35years of age. Consequently, pediatric-to-adult cystic fibrosis care programs would allow suitable preparation time for this transition and develop a standardized group of self-care and management skills.

PMID: 27986495 [PubMed - as supplied by publisher]