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Autoimmunity Reviews Oct 2022Systemic sclerosis (SSc) is a systemic autoimmune disease with heterogeneous clinical presentation and prognosis. JAK inhibitors reduced cutaneous and pulmonary fibrosis... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a systemic autoimmune disease with heterogeneous clinical presentation and prognosis. JAK inhibitors reduced cutaneous and pulmonary fibrosis in mice models of SSc. Clinical data regarding the efficacy and safety of JAK inhibitors in SSc patients are scarce.
METHODS
We performed a systematic literature review of patients with SSc defined by the 2013 ACR/EULAR criteria and treated with JAK inhibitors, searching in Medline, Cochrane library and Embase databases.
RESULTS
Fifty-nine patients (mean age 47 ± 15 years) were included. Median treatment duration was 12 [6-12] months. JAK inhibitors (tofacitinib in 47 patients and baricitinib in 12 patients) were prescribed as first line therapy in 35 patients (59%). A significant cutaneous response (decrease in the mRSS - modified Rodnan skin score - of >5 points and ≥ 25% from baseline) was reported in 52 patients (88%). Among patients with interstitial lung disease (ILD) (n = 31), 28/29 patients had no ILD progression during follow-up time (missing data in 2 patients). Only 2 patients had a disease progression during treatment (including one patient with progressive skin fibrosis). Cutaneous response was more frequently observed in treatment naïve SSc patients. Decrease of the mRSS after treatment initiation was more significant in treatment naïve SSc patients. Eighteen non-serious side-effects were noted in 12 patients (20%), without treatment interruption: 6 infections, 6 gastrointestinal disorders, 4 hepatitis and 3 dyslipidemias.
CONCLUSION
JAK inhibitors could represent a safe and effective treatment option for skin fibrosis and ILD in systemic sclerosis.
Topics: Animals; Fibrosis; Humans; Janus Kinase Inhibitors; Lung Diseases, Interstitial; Mice; Scleroderma, Systemic; Skin Diseases
PubMed: 35944611
DOI: 10.1016/j.autrev.2022.103168 -
BMJ Open Respiratory Research Jun 2023Interstitial lung disease (ILD) is a collective term representing a diverse group of pulmonary fibrotic and inflammatory conditions. Due to the diversity of ILD... (Review)
Review
Interstitial lung disease (ILD) is a collective term representing a diverse group of pulmonary fibrotic and inflammatory conditions. Due to the diversity of ILD conditions, paucity of guidance and updates to diagnostic criteria over time, it has been challenging to precisely determine ILD incidence and prevalence. This systematic review provides a synthesis of published data at a global level and highlights gaps in the current knowledge base. Medline and Embase databases were searched systematically for studies reporting incidence and prevalence of various ILDs. Randomised controlled trials, case reports and conference abstracts were excluded. 80 studies were included, the most described subgroup was autoimmune-related ILD, and the most studied conditions were rheumatoid arthritis (RA)-associated ILD, systemic sclerosis associated (SSc) ILD and idiopathic pulmonary fibrosis (IPF). The prevalence of IPF was mostly established using healthcare datasets, whereas the prevalence of autoimmune ILD tended to be reported in smaller autoimmune cohorts. The prevalence of IPF ranged from 7 to 1650 per 100 000 persons. Prevalence of SSc ILD and RA ILD ranged from 26.1% to 88.1% and 0.6% to 63.7%, respectively. Significant heterogeneity was observed in the reported incidence of various ILD subtypes. This review demonstrates the challenges in establishing trends over time across regions and highlights a need to standardise ILD diagnostic criteria.PROSPERO registration number: CRD42020203035.
Topics: Humans; Prevalence; Incidence; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Arthritis, Rheumatoid
PubMed: 37308252
DOI: 10.1136/bmjresp-2022-001291 -
Journal of Evaluation in Clinical... Apr 2017The 6-minute walk test (6MWT) is widely used as a test of functional exercise capacity. Several studies have reported the minimal clinically important difference (MCID)... (Review)
Review
RATIONALE, AIMS, AND OBJECTIVES
The 6-minute walk test (6MWT) is widely used as a test of functional exercise capacity. Several studies have reported the minimal clinically important difference (MCID) for the 6MWT; however, the findings of the studies have not been examined in the context of one another. In this review, we aimed to summarize available information on the MCID for the 6MWT performed by patients with pathology.
METHODS
Relevant literature was identified by searches of 3 electronic databases (PubMed, Scopus, and Cumulative Index of Nursing and Allied Health), examination of article reference lists, and consultation with an expert. Inclusion necessitated that articles (1) be original, full length, and peer reviewed, (2) report an MCID for the 6MWT, and (3) focus on adults with medical issues. Articles were excluded if the MCID was determined by a procedure other than receiver operating characteristic curve analysis. Articles were abstracted for information on participants, interventions, 6MWT distance, and the determination of MCID. Quality was assessed using a hybrid 9-item (0- to 18-point) instrument.
RESULTS
Six articles were selected based on the inclusion and exclusion criteria. The populations studied included people with chronic obstructive pulmonary disease, lung cancer, coronary artery disease, diffuse parenchymal lung disease, and non-cystic fibrosis bronchiectasis and adults with fear of falling. Mean baseline 6MWT distances ranged from 295 to 551 m. The MCIDs for which the area under the receiver operating characteristic curve was at least 0.70 ranged from 14.0 to 30.5 m.
CONCLUSIONS
Based on our findings, a change of 14.0 to 30.5 m may be clinically important across multiple patient groups.
Topics: Accidental Falls; Bronchiectasis; Coronary Artery Disease; Fear; Humans; Lung Diseases, Interstitial; Minimal Clinically Important Difference; Pulmonary Disease, Chronic Obstructive; Quality of Life; ROC Curve; Walk Test
PubMed: 27592691
DOI: 10.1111/jep.12629 -
International Journal of Molecular... Apr 2023Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use... (Review)
Review
Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Indoles; Pyridones; Treatment Outcome
PubMed: 37175556
DOI: 10.3390/ijms24097849 -
American Journal of Respiratory Cell... Mar 2023Microorganisms colonize the human body. The lungs and respiratory tract, previously believed to be sterile, harbor diverse microbial communities and the genomes of...
Microorganisms colonize the human body. The lungs and respiratory tract, previously believed to be sterile, harbor diverse microbial communities and the genomes of bacteria (bacteriome), viruses (virome), and fungi (mycobiome). Recent advances in amplicon and shotgun metagenomic sequencing technologies and data-analyzing methods have greatly aided the identification and characterization of microbial populations from airways. The respiratory microbiome has been shown to play roles in human health and disease and is an area of rapidly emerging interest in pulmonary medicine. In this review, we provide updated information in the field by focusing on four lung conditions, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis. We evaluate gut, oral, and upper airway microbiomes and how they contribute to lower airway flora. The discussion is followed by a systematic review of the lower airway microbiome in health and disease. We conclude with promising research avenues and implications for evolving therapeutics.
Topics: Humans; Lung; Asthma; Pulmonary Disease, Chronic Obstructive; Microbiota; Cystic Fibrosis
PubMed: 36476129
DOI: 10.1165/rcmb.2022-0208TR -
Chest Nov 2021Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with significant morbidity and mortality. Nintedanib and pirfenidone... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with significant morbidity and mortality. Nintedanib and pirfenidone are two antifibrotic medications currently approved for slowing the rate of lung function decline in IPF, but data on treatment effect on mortality and risk of acute exacerbation (AE) remains limited or unknown.
RESEARCH QUESTION
Does antifibrotic treatment decrease risk of mortality and AE?
STUDY DESIGN AND METHODS
A comprehensive search of several databases, including Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted. Studies were included if they were original articles comparing mortality or AE events in IPF patients with and without antifibrotic treatment. Relative risk (RR) with 95%CI was pooled using random-effects meta-analyses with inverse variance method, assessing two primary outcomes of all-cause mortality and AE risk.
RESULTS
A total of 12,956 patients across 26 studies (eight randomized controlled trials and 18 cohort studies) were included in the meta-analysis. Antifibrotic treatment was associated with decreased risk of all-cause mortality with a pooled RR of 0.55 (95% CI, 0.45-0.66) and I of 82%. This effect was consistent across additional subgroup analyses, including stratification by study type, risk of bias, duration of follow-up, and antifibrotic subtype. Antifibrotic treatment also reduced the risk of AE, with a pooled RR of 0.63 (95% CI, 0.53-0.76), and I of 0%. Effect on AE risk was consistent across subgroup analyses by study type and for nintedanib but not for pirfenidone.
INTERPRETATION
Antifibrotic treatment appears to reduce the risk of all-cause mortality and AE in IPF. Despite greater heterogeneity with pooled analysis, its effect was robust in subgroup analyses by study type, duration of follow-up, and antifibrotic subtype.
Topics: Antifibrotic Agents; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Mortality; Pyridones; Symptom Flare Up; Treatment Outcome
PubMed: 34217681
DOI: 10.1016/j.chest.2021.06.049 -
Journal of Thoracic Disease Mar 2020Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with significant dyspnea and limited exercise capacity. This systematic review aimed to... (Review)
Review
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with significant dyspnea and limited exercise capacity. This systematic review aimed to synthesize evidence of exercise interventions during pulmonary rehabilitation that aim to improve exercise capacity, dyspnea, and health-related quality of life (HRQL) in IPF patients.
METHODS
Searches were performed in MEDLINE, Embase, CENTRAL, SPORTDiscus, PubMed and PEDro from inception to January 2019 using search terms for: (I) participants: 'IPF or interstitial lung disease'; (II) interventions: 'aerobic training or resistance training or respiratory muscle training'; and (III) outcomes: 'exercise capacity or dyspnea or health-related quality of life'. Two reviewers independently screened titles, abstracts and full texts to identify eligible studies. Methodological quality of studies was assessed using the Downs and Black checklist and meta-analyses were performed.
RESULTS
Of 1,677 articles identified, 14 were included (four randomized controlled trials and 10 prospective pre-post design studies) that examined 362 patients receiving training and 95 control subjects. Exercise capacity was measured with the 6-minute walk distance, peak oxygen consumption, peak work rate, or endurance time for constant work rate cycling, which increased after exercise [aerobic exercise; aerobic and breathing exercises; aerobic and inspiratory muscle training (IMT) exercises] compared to the control groups. Dyspnea scores improved after aerobic and breathing exercises. HRQL also improved after aerobic exercise training alone or combined with breathing exercises. Aerobic training alone or combined with IMT or breathing exercises improved exercise capacity.
CONCLUSIONS
Breathing exercises appears to complement exercise training towards improved dyspnea and HRQL in patients with IPF.
PubMed: 32274173
DOI: 10.21037/jtd.2019.12.27 -
American Journal of Respiratory and... Sep 2023Incidental parenchymal abnormalities detected on chest computed tomography scans are termed interstitial lung abnormalities (ILAs). ILAs may represent early... (Meta-Analysis)
Meta-Analysis
Incidental parenchymal abnormalities detected on chest computed tomography scans are termed interstitial lung abnormalities (ILAs). ILAs may represent early interstitial lung disease (ILD) and are associated with an increased risk of progressive fibrosis and mortality. The prevalence of ILAs is unknown, with heterogeneity across study populations. Estimate the pooled prevalence of ILAs in lung cancer screening, general population-based, and at-risk familial cohorts using meta-analysis; identify variables associated with ILA risk; and characterize ILA-associated mortality. The study protocol was registered on PROSPERO (CRD42022373203), and Meta-analyses of Observational Studies in Epidemiology recommendations were followed. Relevant studies were searched on Embase and Medline. Study titles were screened and abstracts reviewed for full-text eligibility. Random effect models were used to pool prevalence estimates for specified subgroups and ILA-associated mortality risk. Risk of ILAs was estimated based on age, sex, and FVC. Quality assessment was conducted using an adapted Assessment Tool for Prevalence Studies. The search identified 9,536 studies, with 22 included, comprising 88,325 participants. The pooled ILA prevalence was 7% (95% confidence interval [CI], 0.01-0.13) in lung cancer screening, 7% (95% CI, 0.04-0.10) in general population, and 26% (95% CI, 0.20-0.32) in familial cohorts. Pooled mortality risk was increased in those with ILAs (odds ratio, 3.56; 95% CI, 2.19-5.81). Older age, male sex, and lower FVC% were associated with greater odds of ILA. Populations undergoing imaging for non-ILD indications demonstrate high ILA prevalence. Standardized reporting and follow-up of ILAs is needed, including defining those at greatest risk of progression to ILD.
Topics: Humans; Male; Adult; Lung; Prevalence; Early Detection of Cancer; Lung Neoplasms; Lung Diseases, Interstitial; Risk Factors
PubMed: 37534937
DOI: 10.1164/rccm.202302-0271OC -
Respiratory Medicine Sep 2023The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) ranges from asymptomatic findings on radiographic imaging to a rapidly progressive illness leading to respiratory failure and death. The treatment is always challenging due to the paucity of proven effective treatments. Nintedanib and pirfenidone are recently approved antifibrotics in idiopathic pulmonary fibrosis. This study aimed to investigate the efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD.
METHODS
Relevant databases were searched for randomized controlled trials that compared pirfenidone or nintedanib with placebo in patients with CTD-ILD and RA-ILD. The primary outcome was the change in forced vital capacity (FVC). The odds ratio or risk ratio with 95% confidence interval (CI) was estimated for categorical data, and the mean difference with 95% CI was estimated for continuous data. The I statistic was used to assess heterogeneity, and meta-analysis was performed when possible.
RESULTS
Ten studies with a total of 880 participants met the inclusion criteria. Of these, four studies were included in the meta-analysis. According to the pooled result, the annual decline of FVC was significantly decreased in the antifibrotic agent arm compared to that in the placebo arm (MD 70.58 mL/yr, 95% CI 40.55 to 100.61).
CONCLUSION
This review suggests a potential benefit and safety of antifibrotic treatment in slowing the decline of FVC in patients with CTD-ILD and RA-ILD. Further large-sample, random-controlled, high-quality trials are needed to provide more evidence in the decision-making regarding the use of antifibrotics in this group of patients.
CLINICAL TRIAL REGISTRATION
PROSPERO; No: CRD42022369112; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Antifibrotic Agents; Lung Diseases, Interstitial; Connective Tissue Diseases; Idiopathic Pulmonary Fibrosis; Vital Capacity
PubMed: 37315742
DOI: 10.1016/j.rmed.2023.107329 -
The Cochrane Database of Systematic... Nov 2019Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation and by temporarily increasing functional residual capacity. The developers of the PEP technique recommend using PEP with a mask in order to avoid air leaks via the upper airways and mouth. In addition, increasing forced residual capacity (FRC) has not been demonstrated using mouthpiece PEP. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. This is an update of a previously published review.
OBJECTIVES
To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2017. Most recent search of the Group's CF Trials Register: 20 February 2019.
SELECTION CRITERIA
Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF. This included, postural drainage and percussion (PDPV), active cycle of breathing techniques (ACBT), oscillating PEP devices, thoracic oscillating devices, bilevel positive airway pressure (BiPaP) and exercise.
DATA COLLECTION AND ANALYSIS
Three authors independently applied the inclusion and exclusion criteria to publications, assessed the risk of bias of the included studies and assessed the quality of the evidence using the GRADE recommendations.
MAIN RESULTS
A total of 28 studies (involving 788 children and adults) were included in the review; 18 studies involving 296 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform any meta-analysis. In 22 of the 28 studies the PEP technique was performed using a mask, in three of the studies a mouthpiece was used with nose clips and in three studies it was unclear whether a mask or mouthpiece was used. These studies compared PEP to ACBT, autogenic drainage (AD), oral oscillating PEP devices, high-frequency chest wall oscillation (HFCWO) and BiPaP and exercise. Forced expiratory volume in one second was the review's primary outcome and the most frequently reported outcome in the studies (24 studies, 716 participants). Single interventions or series of treatments that continued for up to three months demonstrated little or no difference in effect between PEP and other methods of airway clearance on this outcome (low- to moderate-quality evidence). However, long-term studies had equivocal or conflicting results regarding the effect on this outcome (low- to moderate-quality evidence). A second primary outcome was the number of respiratory exacerbations. There was a lower exacerbation rate in participants using PEP compared to other techniques when used with a mask for at least one year (five studies, 232 participants; moderate- to high-quality evidence). In one of the included studies which used PEP with a mouthpiece, it was reported (personal communication) that there was no difference in the number of respiratory exacerbations (66 participants, low-quality evidence). Participant preference was reported in 10 studies; and in all studies with an intervention period of at least one month, this was in favour of PEP. The results for the remaining outcome measures (including our third primary outcome of mucus clearance) were not examined or reported in sufficient detail to provide any high-quality evidence; only very low- to moderate-quality evidence was available for other outcomes. There was limited evidence reported on adverse events; these were measured in five studies, two of which found no events. In a study where infants performing either PEP or PDPV experienced some gastro-oesophageal reflux , this was more severe in the PDPV group (26 infants, low-quality evidence). In PEP versus oscillating PEP, adverse events were only reported in the flutter group (five participants complained of dizziness, which improved after further instructions on device use was provided) (22 participants, low-quality evidence). In PEP versus HFCWO, from one long-term high-quality study (107 participants) there was little or no difference in terms of number of adverse events; however, those in the PEP group had fewer adverse events related to the lower airways when compared to HFCWO (high-certainty evidence). Many studies had a risk of bias as they did not report how the randomisation sequence was either generated or concealed. Most studies reported the number of dropouts and also reported on all planned outcome measures.
AUTHORS' CONCLUSIONS
The evidence provided by this review is of variable quality, but suggests that all techniques and devices described may have a place in the clinical treatment of people with CF. Following meta-analyses of the effects of PEP versus other airway clearance techniques on lung function and patient preference, this Cochrane Review demonstrated that there was high-quality evidence that showed a significant reduction in pulmonary exacerbations when PEP using a mask was compared with HFCWO. It is important to note that airway clearance techniques should be individualised throughout life according to developmental stages, patient preferences, pulmonary symptoms and lung function. This also applies as conditions vary between baseline function and pulmonary exacerbations.
Topics: Cystic Fibrosis; Drainage, Postural; Forced Expiratory Volume; Humans; Mucociliary Clearance; Mucus; Physical Therapy Modalities; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Respiratory Therapy
PubMed: 31774149
DOI: 10.1002/14651858.CD003147.pub5