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1.
PLoS One ; 17(9): e0274349, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36083879

RESUMO

BACKGROUND: Telehealth could enhance rehabilitation for people with chronic health conditions. This review examined the psychometric properties of performance-based measures of physical function administered via telehealth among people with chronic health conditions using the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) approach. METHODS: This systematic review was registered with Prospero (Registration number: CRD42021262547). Four electronic databases were searched up to June 2022. Study quality was evaluated by two independent reviewers using the COSMIN risk of bias checklist. Measurement properties were rated by two independent reviewers in accordance with COSMIN guidance. Results were summarised according to the COSMIN approach and the modified GRADE approach was used to grade quality of the summarised evidence. RESULTS: Five articles met the eligibility criteria. These included patients with Parkinson's Disease (n = 2), stroke (n = 1), cystic fibrosis (n = 1) and chronic heart failure (n = 1). Fifteen performance-based measures of physical function administered via videoconferencing were investigated, spanning measures of functional balance (n = 7), other measures of general functional capacity (n = 4), exercise capacity (n = 2), and functional strength (n = 2). Studies were conducted in Australia (n = 4) and the United States (n = 1). Reliability was reported for twelve measures, with all twelve demonstrating sufficient inter-rater and intra-rater reliability. Criterion validity for all fifteen measures was reported, with eight demonstrating sufficient validity and the remaining seven demonstrating indeterminate validity. No studies reported data on measurement error or responsiveness. CONCLUSIONS: Several performance-based measures of physical function across the domains of exercise capacity, strength, balance and general functional capacity may have sufficient reliability and criterion validity when administered via telehealth. However, the evidence is of low-very low quality, reflecting the small number of studies conducted and the small sample sizes included in the studies. Future research is needed to explore the measurement error, responsiveness, interpretability and feasibility of these measures administered via telehealth.


Assuntos
Lista de Checagem , Telemedicina , Consenso , Humanos , Psicometria , Reprodutibilidade dos Testes
2.
Cochrane Database Syst Rev ; 9: CD002204, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053129

RESUMO

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. OBJECTIVES: The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials. SELECTION CRITERIA: Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The searches identified six trials; none of which met the inclusion criteria for the review. MAIN RESULTS: We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update. AUTHORS' CONCLUSIONS: At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.


Assuntos
Aspergilose Broncopulmonar Alérgica , Fibrose Cística , Antifúngicos/uso terapêutico , Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergillus fumigatus , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Humanos , Itraconazol/uso terapêutico
3.
Cochrane Database Syst Rev ; 9: CD002202, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047926

RESUMO

BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising foetal haemoglobin (HbF). This is an update of a previously published Cochrane Review. OBJECTIVES: The aims of this review are to determine through a review of randomised or quasi-randomised studies whether the use of hydroxyurea in people with SCD alters the pattern of acute events, including pain; prevents, delays or reverses organ dysfunction; alters mortality and quality of life; or is associated with adverse effects. In addition, we hoped to assess whether the response to hydroxyurea in SCD varies with the type of SCD, age of the individual, duration and dose of treatment, and healthcare setting. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. The date of the most recent search was 17 February 2022. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials (RCTs and quasi-RCTs), of one month or longer, comparing hydroxyurea with placebo or standard therapy in people  with SCD. DATA COLLECTION AND ANALYSIS: Authors independently assessed studies for inclusion, carried out data extraction, assessed the risk of bias and assessed the quality of the evidence using GRADE. MAIN RESULTS: We included nine RCTs recruiting 1104 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sߺthalassaemia (HbSߺthal) genotypes). Studies lasted from six to 30 months. We judged the quality of the evidence for the first two comparisons below as moderate to low as the studies contributing to these comparisons were mostly large and well-designed (and at low risk of bias); however, the evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events, and the results are applicable only to individuals with HbSS and HbSߺthal genotypes. We judged the quality of the evidence for the third and fourth comparisons to be very low due to the limited number of participants, the lack of statistical power (both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. Hydroxyurea versus placebo Five studies (784 adults and children with HbSS or HbSߺthal) compared hydroxyurea to placebo; four recruited individuals with only severe disease and one recruited individuals with all disease severities. Hydroxyurea probably improves pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use) and life-threatening illness, but we found no difference in death rates (10 deaths occurred during the studies, but the rates did not differ by treatment group) (all moderate-quality evidence). Hydroxyurea may improve measures of HbF (low-quality evidence) and probably decreases neutrophil counts (moderate-quality evidence). There were no consistent differences in terms of quality of life and adverse events (including serious or life-threatening events) (low-quality evidence). There were fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups.  Hydroxyurea and phlebotomy versus transfusion and chelation Two studies (254 children with HbSS or HbSߺthal also with risk of primary or secondary stroke) contributed to this comparison. There were no consistent differences in terms of pain alteration, death or adverse events (low-quality evidence) or life-threatening illness (moderate-quality evidence). Hydroxyurea with phlebotomy probably increased HbF and decreased neutrophil counts (moderate-quality evidence), but there were more occurrences of acute chest syndrome and infections. Quality of life was not reported. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.  Hydroxyurea versus observation One study (22 children with HbSS or HbSߺthal also at risk of stoke) compared hydroxyurea to observation. Pain alteration and quality of life were not reported. There were no differences in life-threatening illness, death (no deaths reported in either group) or adverse events (very low-quality evidence). We are uncertain if hydroxyurea improves HbF or decreases neutrophil counts (very low-quality evidence). Treatment regimens with and without hydroxyurea One study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea. Pain alteration, life-threatening illness and quality of life were not reported. There were no differences in death rates (no deaths reported in either group), adverse events or neutrophil levels (very low-quality evidence). We are uncertain if hydroxyurea improves HbF (very low-quality evidence). AUTHORS' CONCLUSIONS: There is evidence to suggest that hydroxyurea may be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSߺthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial Doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with the HbSC genotype. Future studies should be designed to address such uncertainties.


Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Acidente Vascular Cerebral , Síndrome Torácica Aguda/induzido quimicamente , Síndrome Torácica Aguda/complicações , Síndrome Torácica Aguda/tratamento farmacológico , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/efeitos adversos , Criança , Hemoglobina Falciforme/uso terapêutico , Humanos , Hidroxiureia/efeitos adversos , Dor/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle
4.
Ther Adv Respir Dis ; 16: 17534666221122572, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36066081

RESUMO

BACKGROUND: Airway clearance techniques (ACTs) are integral to cystic fibrosis (CF) management. However, there is no consensus as to which outcome measures (OMs) are best for assessing ACT efficacy. OBJECTIVES: To summarise OMs that have been assessed for their clinimetric properties (including validity, feasibility, reliability, and reproducibility) within the context of ACT research in CF. DESIGN AND METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) standards. Any parallel or cross-over randomised controlled trial (RCT) investigating outcome measures for ACT in the CF population were eligible for inclusion. The search was performed in five medical databases, clinicaltrials.gov, and abstracts from international CF conferences. The authors planned to independently assess study quality and risk of bias using the COnsensus-based Standards for the selection of health status Measurement InstrumeNts (COSMIN) risk of bias checklist with external validity assessment based upon study details (participants and study intervention). Two review authors (GS and MJ) independently screened search results against inclusion criteria, and further data extraction were planned but not required. RESULTS: No completed RCTs from the 187 studies identified met inclusion criteria for the primary or post hoc secondary objective. Two ongoing trials were identified. DISCUSSION AND CONCLUSION: This empty systematic review highlights that high-quality RCTs are urgently needed to investigate and validate the clinimetric properties of OMs used to assess ACT efficacy. With the changing demographics of CF combined with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, an accurate assessment of the current benefit of ACT or the effect of ACT withdrawal is a high priority for clinical practice and future research; OMs which have been validated for this purpose are essential. REGISTRATION: This systematic review was registered on the PROSPERO database (CRD42020206033).


Assuntos
Fibrose Cística , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Humanos , Avaliação de Resultados em Cuidados de Saúde
5.
Cochrane Database Syst Rev ; 9: CD008190, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36149378

RESUMO

BACKGROUND: Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review. OBJECTIVES: To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses. MAIN RESULTS: We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias.  Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome.   Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV1) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence).  Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months.  AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.


Assuntos
Fibrose Cística , Adulto , Anorexia/induzido quimicamente , Anorexia/tratamento farmacológico , Antibacterianos/uso terapêutico , Estimulantes do Apetite/uso terapêutico , Criança , Ciproeptadina/uso terapêutico , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Humanos , Acetato de Megestrol/uso terapêutico , Qualidade de Vida
6.
PLoS One ; 17(8): e0272091, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35944004

RESUMO

INTRODUCTION: Cystic fibrosis (CF) is a hereditary autosomal recessive disorder caused by a range of mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. This gene encodes the CFTR protein, which acts as a chloride channel activated by cyclic AMP (cAMP). This meta-analysis aimed to compare the responsiveness of induced pluripotent stem cells (iPSCs) to cAMP analogues to that of commonly used animal models. METHODS: Databases searched included PubMed, Scopus, and Medline from inception to January 2020. A total of 8 and 3 studies, respectively, for animal models and iPSCs, were analyzed. Studies were extracted for investigating cAMP-stimulated anion transport by measuring the short circuit current (Isc) of chloride channels in different animal models and iPSC systems We utilized an inverse variance heterogeneity model for synthesis. RESULTS: Our analysis showed considerable heterogeneity in the mean Isc value in both animal models and iPSCs studies (compared to their WT counterparts), and both suffer from variable responsiveness based on the nature of the underlying model. There was no clear advantage of one over the other. CONCLUSIONS: Studies on both animal and iPSCs models generated considerable heterogeneity. Given the potential of iPSC-derived models to study different diseases, we recommend paying more attention to developing reproducible models of iPSC as it has potential if adequately developed.


Assuntos
Fibrose Cística , Células-Tronco Pluripotentes Induzidas , Animais , Canais de Cloreto/metabolismo , AMP Cíclico/metabolismo , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Modelos Animais
7.
Respir Res ; 23(1): 214, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999634

RESUMO

BACKGROUND: While there seems to be a consensus that a decrease in gut microbiome diversity is related to a decline in health status, the associations between respiratory microbiome diversity and chronic lung disease remain a matter of debate. We provide a systematic review and meta-analysis of studies examining lung microbiota alpha-diversity in patients with asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) or bronchiectasis (NCFB), in which a control group based on disease status or healthy subjects is provided for comparison. RESULTS: We reviewed 351 articles on title and abstract, of which 27 met our inclusion criteria for systematic review. Data from 24 of these studies were used in the meta-analysis. We observed a trend that CF patients have a less diverse respiratory microbiota than healthy individuals. However, substantial heterogeneity was present and detailed using random-effects models, which limits the comparison between studies. CONCLUSIONS: Knowledge on respiratory microbiota is under construction, and for the moment, it seems that alpha-diversity measurements are not enough documented to fully understand the link between microbiota and health, excepted in CF context which represents the most studied chronic respiratory disease with consistent published data to link alpha-diversity and lung function. Whether differences in respiratory microbiota profiles have an impact on chronic respiratory disease symptoms and/or evolution deserves further exploration.


Assuntos
Bronquiectasia , Fibrose Cística , Microbioma Gastrointestinal , Microbiota , Transtornos Respiratórios , Bronquiectasia/diagnóstico , Humanos , Pulmão
8.
Cureus ; 14(7): e27132, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36017299

RESUMO

Selective phosphodiesterase 4 (PDE4) inhibitors have been extensively studied for the treatment of various respiratory diseases due to their broad anti-inflammatory and/or bronchodilator effects. Roflumilast, an oral selective PDE4 inhibitor, is currently used as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) with chronic bronchitis. Despite its proven efficacy in other respiratory disorders, including asthma, no other PDE4 inhibitor is approved for respiratory pathologies. This systematic review summarizes the therapeutic action of PDE4 inhibitors, their limitations, recent therapeutic success, and future targets for their use in respiratory diseases other than COPD. An electronic literature search was conducted on four databases, namely, PubMed, PubMed Central, Google Scholar, and ScienceDirect, to collect data on related studies done in humans and published in the English language in the last five years. After extensive analysis and quality appraisal, 11 studies were eligible and thus included in this review, consisting of two randomized controlled trials (RCT), one systematic review and meta-analysis, and eight literature reviews. Roflumilast is not approved for the treatment of asthma due to associated adverse effects and comparable efficacy to inhaled corticosteroids, which are considered the mainstay of asthma maintenance therapy. Hence, the importance of balancing the efficacy with minimizing the side effects is highlighted. Tanimilast (CHF6001), an inhalational selective PDE4 inhibitor, and ensifentrine, a combined PDE3/4 inhibitor, demonstrate the recent therapeutic success in asthma and warrant further large-scale clinical studies. Future researchers will focus on the specific endotype than the phenotype in asthma as a meaningful therapeutic approach due to the high heterogeneity noted in asthma. Current evidence suggests the possibility of PDE4 inhibitors as a novel therapeutic option for chronic cough, allergic rhinitis, and cystic fibrosis. Further evidence from new studies is eagerly anticipated to better understand the efficacy and safety of PDE4 inhibitors in these respiratory diseases.

9.
Cochrane Database Syst Rev ; 8: CD008319, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914011

RESUMO

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work, and improves their long-term lung function. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 7 March 2022. We also searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 3 May 2022. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the certainty of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information. MAIN RESULTS: Five trials with 183 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and three trials (106 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials but, for four out of five trials, we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis. One trial was a cross-over design and we only included data from the first intervention arm. Inhaled antibiotics alone versus intravenous antibiotics alone Only one trial (18 participants) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-certainty evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-certainty evidence). With regards to our secondary outcomes, one trial (18 participants) reported no difference in the need for additional antibiotics and the second trial (59 participants) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-certainty evidence). The single trial (18 participants) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-certainty  evidence). Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics alone Inhaled antibiotics plus intravenous antibiotics may make little or no difference to quality of life compared to intravenous antibiotics alone. None of the trials reported time off work or school. All three trials measured lung function, but found no difference between groups in forced expiratory volume in one second (two trials; 44 participants; very low-certainty evidence) or vital capacity (one trial; 62 participants). None of the trials reported on the need for additional antibiotics. Inhaled plus intravenous antibiotics may make little difference to the time to next exacerbation; however, one trial (28 participants) reported on hospital admissions and found no difference between groups. There is likely no difference between groups in adverse events (very low-certainty evidence) and one trial (62 participants) reported no difference in the emergence of antibiotic-resistant organisms (very low-certainty evidence). AUTHORS' CONCLUSIONS: We identified only low- or very low-certainty evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.


Assuntos
Antibacterianos , Fibrose Cística , Administração por Inalação , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Humanos , Pulmão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tobramicina/administração & dosagem , Tobramicina/uso terapêutico
10.
Respir Med ; 201: 106937, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35926429

RESUMO

BACKGROUND: Non cystic fibrosis, non primary ciliary dyskinesia bronchiectasis (nCFnPCD-BE) results in significant morbidity with few evidence-based treatments. OBJECTIVE: assessments are required to assess severity and evaluate treatment. Lung clearance index (LCI) measures ventilation inhomogeneity and is a sensitive test of disease in CF; its use in nCFnPCD-BE is unclear. METHODS: A systematic review of LCI in nCFnPCD-BE was performed using standard methodology (protocol registered on PROSPERO, University of York). RESULTS: Of 276 records identified, 12 articles, describing 519 adult and paediatric patients in cross-sectional studies were included, addressing several domains. 1: What is the utility of LCI in detecting disease and severity? LCI detected disease in adults, differentiating bronchiectasis from controls (AUC 0.90 to 0.96) and mild from moderate/severe bronchiectasis on CT (AUC 0.73). 2: Does LCI correlate with spirometry and imaging? LCI correlated with spirometry in adult (r = -0.37 to -0.61) and paediatric (r = -0.6) groups, signs of bronchiectasis on CT, and CT scoring systems (modified Reiff). 3: Does LCI relate to subjective scores of severity? In adults, LCI correlated with St. George's Respiratory Questionnaire (r = 0.18) and Bronchiectasis Severity Index (r = 0.45). 4: Does LCI identify response to intervention? LCI did not change in studies examining LCI pre-post intervention (adults treated for exacerbation and undergoing physiotherapy). Overall study quality was variable. CONCLUSION: Contrary to data in CF, the review did not identify good quality studies defining the role of LCI in children with bronchiectasis. In adults, LCI was a sensitive measure of disease severity and correlated with clinical assessment tools.


Assuntos
Bronquiectasia , Transtornos da Motilidade Ciliar , Adulto , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/patologia , Criança , Estudos Transversais , Fibrose , Volume Expiratório Forçado/fisiologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia
11.
BMJ Open ; 12(8): e055672, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914904

RESUMO

OBJECTIVE: To accurately estimate the global prevalence of non-tuberculous mycobacteria (NTM) in adults with non-cystic fibrosis (non-CF) bronchiectasis and to determine the proportion of NTM species and subspecies in clinical patients from 2006 to 2021. DESIGN: Systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Medline, Embase, Cochrane Library and Web of Science were searched for articles published between 2006 and 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included all the prospective or retrospective studies without language restrictions and all patients were adults (≥18 years of age) with non-CF bronchiectasis. The studies estimated the effect size of the prevalence of NTM with a sample size ≥40, and patients were registered in and after 2006. DATA EXTRACTION AND SYNTHESIS: Two reviewers screened the titles, abstracts and full texts independently. Relevant information was extracted and curated into tables. Risk of bias was evaluated following the Cochrane Collaboration's tool. Meta-analysis was performed with software R Statistics V.3.6.3 using random effect model with 95% CI. I2 index and Q statistics were calculated to assess the heterogeneity, and mixed-effects meta-regression analyses were performed to identify the sources of heterogeneity. The proportions of NTM subspecies were examined using Shapiro-Wilk normality test in R. RESULTS: Of all the 2014 studies yielded, 24 met the inclusion criteria. Of these, 14 were identified to be randomised controlled studies and included for an accurate estimation. The global prevalence of NTM in adults with non-CF bronchiectasis from 2006 to 2021 was estimated to be approximately 10%, with great variations primarily due to geographical location. Mycobacterium avium complex was the most common subspecies, followed by Mycobacterium simiae and Mycobacterium gordonae. CONCLUSIONS: The prevalence of NTM in adults with non-CF bronchiectasis has been on the rise and the most common subspecies changed greatly in recent years. More cohort studies should be done in many countries and regions for future estimates. PROSPERO REGISTRATION NUMBER: CRD42020168473.


Assuntos
Bronquiectasia , Micobactérias não Tuberculosas , Adulto , Bronquiectasia/epidemiologia , Bronquiectasia/microbiologia , Fibrose , Humanos , Prevalência , Estudos Prospectivos , Estudos Retrospectivos
12.
Front Pediatr ; 10: 958658, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003489

RESUMO

Background: People with cystic fibrosis (CF) are considered a clinically fragile population with an intrinsic higher risk of developing severe COVID-19, though a certain variability in terms of outcomes and hospitalization has been noticed. Aim: To highlight the main risk factors for severe COVID-19 in patients with CF. Methods: A systematic review of the current literature was conducted through PubMed and EMBASE databases. English-written articles reporting clinical data on CF subjects with SARS-CoV2 infection were included and analyzed. Selected reports were evaluated for adherence to STROBE recommendations. Results: After the selection phase, 9 observational studies were included, 5 of which reported data from CF Registry Global Harmonization Group. The hospitalization rate ranged from 18.2 to 58.1%. The main risk factors for severe outcome were as follows: FEV1 < 70%p, CF-related diabetes, age > 40 years, pancreatic insufficiency, underweight, previous transplant, azithromycin use. Use of dornase alfa was associated with decreased risk for severe disease, while there was insufficient evidence to establish the role of inhaled steroids or CFTR modulators. No solid data regarding specific SARS-CoV-2 therapies in patients with CF emerged. Conclusion: Most people with CF experience a mild course of SARS-CoV-2 infection, nevertheless subgroups with higher risk of severe outcome emerged. Maintenance therapies for CF overall did not show a clear preventive effect against severe outcomes, although dornase alfa seems to give some protection. Due to the current lack of data on specific COVID-19 therapies and immunization in patients with CF, further studies are needed to establish their impact in this population.

13.
J Cyst Fibros ; 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36008229

RESUMO

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes. METHODS: We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included. RESULTS: Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7). CONCLUSIONS: CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.

14.
JBI Evid Synth ; 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35975314

RESUMO

OBJECTIVE: The objective of this review is to determine the incidence and prevalence, clinical features, and outcomes of COVID-19 in persons with cystic fibrosis. INTRODUCTION: Cystic fibrosis, predominantly a chronic respiratory illness, has long been known to be fatal with concomitant bacterial or viral infections. However, the effects of COVID-19 on this protracted disease need to be understood, especially since the major manifestations affect the respiratory system. Hence, the burden, clinical features, and outcomes of COVID-19 on individuals with cystic fibrosis need to be understood. INCLUSION CRITERIA: This review will consider studies on persons in all age groups with preexisting cystic fibrosis who are diagnosed with COVID-19 using either a polymerase chain reaction, serology, or point-of-care test for SARS-CoV-2. METHODS: JBI methodology for systematic reviews of prevalence and incidence will be used for this review. A methodical search for eligible studies in English (as well as available translations) in MEDLINE, Embase, Scopus, and CINAHL, and unpublished literature in Google Scholar, Dissertation Abstracts International, ProQuest Dissertations and Theses, and MedNar will be conducted from the year 2020 onwards. Studies meeting the inclusion criteria will be selected for appraisal and their methodological quality will be assessed by two independent reviewers based on study titles and abstracts, followed by full-text review focusing on sampling and statistical analysis. Data extraction will be accomplished using a standardized tool. If adequate synthesized data are obtained, a meta-analysis will be conducted; otherwise, the findings will be presented in a narrative format, including tables and figures to aid in data presentation where appropriate. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021237792.

15.
Cochrane Database Syst Rev ; 8: CD002768, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943025

RESUMO

BACKGROUND: Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published review. OBJECTIVES: To assess the effects of physical activity interventions on exercise capacity by peak oxygen uptake, lung function by forced expiratory volume in one second (FEV1), health-related quality of life (HRQoL) and further important patient-relevant outcomes in people with cystic fibrosis (CF). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The most recent search was on 3 March 2022. We also searched two ongoing trials registers: clinicaltrials.gov, most recently on 4 March 2022; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), most recently on 16 March 2022.  SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs comparing physical activity interventions of any type and a minimum intervention duration of two weeks with conventional care (no physical activity intervention) in people with CF. DATA COLLECTION AND ANALYSIS: Two review authors independently selected RCTs for inclusion, assessed methodological quality and extracted data. We assessed the certainty of the evidence using GRADE.  MAIN RESULTS: We included 24 parallel RCTs (875 participants). The number of participants in the studies ranged from nine to 117, with a wide range of disease severity. The studies' age demographics varied: in two studies, all participants were adults; in 13 studies, participants were 18 years and younger; in one study, participants were 15 years and older; in one study, participants were 12 years and older; and seven studies included all age ranges. The active training programme lasted up to and including six months in 14 studies, and longer than six months in the remaining 10 studies. Of the 24 included studies, seven implemented a follow-up period (when supervision was withdrawn, but participants were still allowed to exercise) ranging from one to 12 months. Studies employed differing levels of supervision: in 12 studies, training was supervised; in 11 studies, it was partially supervised; and in one study, training was unsupervised. The quality of the included studies varied widely. This Cochrane Review shows that, in studies with an active training programme lasting over six months in people with CF, physical activity probably has a positive effect on exercise capacity when compared to no physical activity (usual care) (mean difference (MD) 1.60, 95% confidence interval (CI) 0.16 to 3.05; 6 RCTs, 348 participants; moderate-certainty evidence). The magnitude of improvement in exercise capacity is interpreted as small, although study results were heterogeneous. Physical activity interventions may have no effect on lung function (forced expiratory volume in one second (FEV1) % predicted) (MD 2.41, 95% CI ‒0.49 to 5.31; 6 RCTs, 367 participants), HRQoL physical functioning (MD 2.19, 95% CI ‒3.42 to 7.80; 4 RCTs, 247 participants) and HRQoL respiratory domain (MD ‒0.05, 95% CI ‒3.61 to 3.51; 4 RCTs, 251 participants) at six months and longer (low-certainty evidence). One study (117 participants) reported no differences between the physical activity and control groups in the number of participants experiencing a pulmonary exacerbation by six months (incidence rate ratio 1.28, 95% CI 0.85 to 1.94) or in the time to first exacerbation over 12 months (hazard ratio 1.34, 95% CI 0.65 to 2.80) (both high-certainty evidence); and no effects of physical activity on diabetic control (after 1 hour: MD ‒0.04 mmol/L, 95% CI ‒1.11 to 1.03; 67 participants; after 2 hours: MD ‒0.44 mmol/L, 95% CI ‒1.43 to 0.55; 81 participants; moderate-certainty evidence). We found no difference between groups in the number of adverse events over six months (odds ratio 6.22, 95% CI 0.72 to 53.40; 2 RCTs, 156 participants; low-certainty evidence). For other time points (up to and including six months and during a follow-up period with no active intervention), the effects of physical activity versus control were similar to those reported for the outcomes above. However, only three out of seven studies adding a follow-up period with no active intervention (ranging between one and 12 months) reported on the primary outcomes of changes in exercise capacity and lung function, and one on HRQoL. These data must be interpreted with caution. Altogether, given the heterogeneity of effects across studies, the wide variation in study quality and lack of information on clinically meaningful changes for several outcome measures, we consider the overall certainty of evidence on the effects of physical activity interventions on exercise capacity, lung function and HRQoL to be low to moderate. AUTHORS' CONCLUSIONS: Physical activity interventions for six months and longer likely improve exercise capacity when compared to no training (moderate-certainty evidence). Current evidence shows little or no effect on lung function and HRQoL (low-certainty evidence). Over recent decades, physical activity has gained increasing interest and is already part of multidisciplinary care offered to most people with CF. Adverse effects of physical activity appear rare and there is no reason to actively discourage regular physical activity and exercise. The benefits of including physical activity in an individual's regular care may be influenced by the type and duration of the activity programme as well as individual preferences for and barriers to physical activity. Further high-quality and sufficiently-sized studies are needed to comprehensively assess the benefits of physical activity and exercise in people with CF, particularly in the new era of CF medicine.


Assuntos
Fibrose Cística , Adolescente , Adulto , Fibrose Cística/tratamento farmacológico , Exercício Físico , Volume Expiratório Forçado , Humanos , Qualidade de Vida
16.
Eur Respir Rev ; 31(165)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35896271

RESUMO

BACKGROUND: Aspergillus fumigatus is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF. OBJECTIVE: To systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF. METHODS: A systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932). RESULTS: A total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA. CONCLUSION: Scientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.


Assuntos
Aspergilose Broncopulmonar Alérgica , Produtos Biológicos , Fibrose Cística , Adulto , Antifúngicos/efeitos adversos , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Criança , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Humanos , Revisões Sistemáticas como Assunto
17.
J Adv Nurs ; 78(10): 3159-3173, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35819171

RESUMO

AIMS: To synthesize qualitative studies of subjective experience of pregnancy in people with cystic fibrosis. DESIGN: Thematic synthesis of qualitative studies. DATA SOURCES: We searched PUBMED, CINAHL, EMBASE. PsicINFO and Social Sciences Citation Index for qualitative studies published in English, which reported on pregnancy in people with cystic fibrosis. Searches were carried out in March 2021, updated in June 2022. REVIEW METHODS: Studies that met the inclusion criteria were appraised for quality using the Critical Appraisal Skills Programme (CASP) for qualitative research. Data were extracted from the studies, analyse and synthesise using thematic synthesis approach. RESULTS: Thirteen studies were included in the review and 'Walking on a wire' framework was conceptualized. We found three analytical themes: (1) desire for information related to pregnancy in cystic fibrosis, (2) factors at play in decision-making related to pregnancy for people with cystic fibrosis and (3) pregnancy experience and eight descriptive themes: (1) information topics, (2) CF healthcare team/PwCF as a provider of reproductive health information, (3) information timing, (4) barriers to information delivery, (5) barriers to decision-making and stresses relating to the process of trying to conceive, (6) environmental factors, (7) coping with challenges, and (8) moving towards parenthood. CONCLUSION: For people with cystic fibrosis, pregnancy is a complex pathway: the amount of knowledge about cystic fibrosis and sexual and reproductive health, barriers to pregnancy and environmental factors provides the background to decision-making. Moreover, coping with pregnancy is a challenging experience, where they have to mediate between the physical and emotional implications of planning a pregnancy and the limitations imposed by the chronic health conditions. IMPACT: Understanding the psychological experiences of people with cystic fibrosis (PwCF) will improve future research and practice. Education about sexual and reproductive health and psychosocial care programmes are necessary to help PwCF deal with the challenges related to pregnancy. Hospitals should enhance the development of specific programmes to promote the well-being of individuals with CF who are planning a pregnancy.


Assuntos
Fibrose Cística , Feminino , Humanos , Equipe de Assistência ao Paciente , Gravidez , Pesquisa Qualitativa
18.
Respir Investig ; 60(5): 625-632, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35811289

RESUMO

BACKGROUND: Bronchiectasis is a cause of increased morbidity of the respiratory system. Exacerbations among patients with non-CF (cystic fibrosis) bronchiectasis result in reduced pulmonary function and poor quality of life. While the role of bacteria in triggering exacerbations in patients with non- CF bronchiectasis has been well studied, little is known about viral infections in these patients. We aimed to review the evidence on the role of respiratory viruses in the exacerbations of non-CF bronchiectasis. METHODS: Relevant literature was searched on the MEDLINE/PubMed database. Seven studies satisfied the criteria and were included in this review. RESULTS: According to the included articles, respiratory viruses are often identified in exacerbations of patients with non-CF bronchiectasis with the most frequent being human rhinovirus and influenza viruses. When a virus is isolated during an exacerbation patients have more symptoms from the upper respiratory tract. One study showed that detection of Epstein- Barr virus among patients with non-CF bronchiectasis is correlated with faster reduction of pulmonary function and progression of the disease. CONCLUSION: Viruses seem to have a role in the exacerbation of patients with non-CF bronchiectasis. However, the exact nature and importance of this role remain elusive. Viruses are also isolated during the stable period of the disease. Further well-designed studies are necessary to clarify this complex issue.


Assuntos
Bronquiectasia , Fibrose Cística , Viroses , Antibacterianos , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose , Humanos , Pulmão , Qualidade de Vida , Viroses/complicações , Viroses/diagnóstico
19.
Front Pediatr ; 10: 937250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844763

RESUMO

Background and Aim: Cystic fibrosis (CF) is a genetic disease that is difficult to treat and caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Small molecules have been used to treat the symptom caused by CFTR mutations by restoring CFTR protein function. However, the data on children with CF are scarce. This meta-analysis aimed to evaluate the effectiveness and safety of this therapy in children diagnosed with CF. Materials and Methods: Relevant studies were identified through searching medical databases before April 1, 2022. The primary outcomes of ppFEV1, lung clearance index2.5 (LCI2.5), sweat chloride concentration (SwCI), and Cystic Fibrosis Questionnaire-Revised (CFQ-R) score were pooled and analyzed. The secondary outcomes were nutritional status (weight, BMI, stature, and their z-score) and adverse events under therapy. Results: A total of twelve studies were included. Compared with the placebo group, the pooled outcome of the ppFEV1, LCI2.5, SwCI, and CFQ-R score were improved by 7.91 {[95% confidence interval (CI), 3.71-12.12], -1.00 (95% CI, -1.38 to -0.63), -35.22 (95% CI, -55.51 to -14.92), and 4.45 (95% CI, 2.31-6.59), respectively}. Compared with the placebo group, the pooled result of the change in weight was improved by 1.53 (95% CI, 0.42-2.63). All the aforementioned results were also improved in single-arm studies. No clear differences in adverse events were found between CFTR modulator therapy and the placebo group. Conclusion: CFTR modulators could improve multiaspect function in children with CF and result in comparable adverse events.

20.
Cochrane Database Syst Rev ; 7: CD011808, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35802341

RESUMO

BACKGROUND: In people with sickle cell disease, sickled red blood cells cause the occlusion of small blood vessels, which presents as episodes of severe pain known as pain crises or vaso-occlusive crises. The pain can occur in the bones, chest, or other parts of the body, and may last several hours to days. Pain relief during crises includes both pharmacologic and non-pharmacologic treatments. The efficacy of inhaled nitric oxide in pain crises has been a subject of controversy; hypotheses have been made suggesting a beneficial response due to its vasodilator properties, yet no conclusive evidence has been presented. This review aimed to evaluate the available randomised controlled studies addressing this topic. OBJECTIVES: To capture the body of evidence evaluating the efficacy and safety of the use of inhaled nitric oxide in treating pain crises in people with sickle cell disease, and to assess the relevance, robustness, and validity of the treatment to better guide medical practice in the fields of haematology and palliative care (since the recent literature seems to favour the involvement of palliative care for such people). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register. We searched for unpublished work in the abstract books of the European Haematology Association conference, the American Society of Hematology conference, the British Society for Haematology Annual Scientific Meeting, the Caribbean Health Research Council Meetings, and the National Sickle Cell Disease Program Annual Meeting. The most recent search was conducted on 1 September 2021. We also searched ongoing study registries on 19 November 2021. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing inhaled nitric oxide with placebo for treating pain crises in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data (including adverse event data), with any disagreements resolved by consulting a third review author. When the data were not reported in the text, we attempted to extract the data from available tables or figures. We contacted trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria. MAIN RESULTS: We included three trials involving a total of 188 participants in the review. There were equal numbers of males and females. Most participants were adults, although one small trial was conducted in a children's hospital and recruited children over the age of 10 years. All three parallel trials compared inhaled nitric oxygen (80 parts per million (ppm)) to placebo (nitrogen gas mixed with oxygen or room air) for four hours; one trial continued administering nitric oxide (40 ppm) for a further four hours. This extended trial had an overall low risk of bias; however, we had concerns about risk of bias for the remaining two trials due to their small sample size, and additionally a high risk of bias due to financial conflicts of interest in one of these smaller trials. We were only able to analyse some limited data from the eight-hour trial, reporting the remaining results narratively. Evidence from one trial (150 participants) suggested that inhaled nitric oxide may not reduce the time to pain resolution: inhaled nitric oxide median 73.0 hours (95% confidence interval (CI) 46.0 to 91.0) and with placebo median 65.5 hours (95% CI 48.1 to 84.0) (low-certainty evidence). No trial reported on the duration of the initial pain crisis. Only one large trial reported on the frequency of pain crises in the follow-up period and found there may be little or no difference between the inhaled nitric oxide and placebo groups for return to the emergency department (risk ratio (RR) 0.73, 95% CI 0.31 to 1.71) and rehospitalisation (RR 0.53, 95% CI 0.25 to 1.11) (150 participants; low-certainty evidence). There may be little or no difference between treatment and placebo in terms of reduction in pain score at any time point up to eight hours (150 participants). The two smaller trials reported a beneficial effect of inhaled nitric oxide in reducing the visual analogue pain score after four hours of the intervention. Analgesic use was reported not to differ greatly between the inhaled nitric oxide group and placebo group in any of the three trials, but no analysable data were provided. Two trials reported the median duration of hospitalisation: in the largest trial the placebo group had the shorter duration, whilst in the second smaller (paediatric) trial hospitalisation was shorter in the treatment group. Only the largest trial (150 participants) reported serious adverse events, with no increase in the inhaled nitric oxide group during or after the intervention compared to the control group (acute chest syndrome occurred in 5 out of 75 participants from each group, pyrexia in 1 out of 75 participants from each group, and dysphagia and a drop in haemoglobin were each reported in 1 out of 75 participants in the inhaled nitric oxide group) (low-certainty evidence). AUTHORS' CONCLUSIONS: The currently available evidence is insufficient to determine the effects (benefits or harms) of using inhaled nitric oxide to treat pain (vaso-occlusive) crises in people with sickle cell disease. Large-scale, long-term trials are needed to provide more robust data in this area. Patient-important outcomes (e.g. measures of pain and time to pain resolution and amounts of analgesics used), as well as use of healthcare services, should be measured and reported in a standardised manner.


Assuntos
Anemia Falciforme , Óxido Nítrico , Adulto , Analgésicos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Óxido Nítrico/uso terapêutico , Oxigênio , Dor/tratamento farmacológico , Dor/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
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