Pirfenidone is a novel antifibrotic drug for the treatment of mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, adverse events may offset treatment benefits and compliance.
To assess ...recent course of disease, adverse events and compliance in patients who started pirfenidone.
In an observational cohort study, 63 patients with mild-to-moderate IPF who started pirfenidone between May 2011 and June 2013 were reviewed. Pulmonary function, adverse events and treatment compliance were recorded at each clinic visit. Disease progression was defined as a reduction of vital capacity ≥10% and/or diffusion capacity (DLCO) ≥15%.
Follow-up time on pirfenidone treatment was 11 (±7) months. Sixty-six percent of the patients continued with pirfenidone monotherapy and 34% of the patients received pirfenidone combined with corticosteroids (CCS) and/or N-acetylcysteine (NAC). There was a nonsignificant reduction in mean decline of percent predicted forced vital capacity after treatment start (0.7 ± 10.9%) compared to the pretreatment period (6.6 ± 6.7%, p = 0.098). Sixty-two percent of the patients had stable disease on pirfenidone treatment. Adverse events affected 85% of the patients, leading to discontinuation of pirfenidone in 20%. Adverse events and treatment discontinuation were seen more frequently in patients with concomitant CCS and/or NAC treatment.
Adverse events affect the majority of patients treated with pirfenidone, but are mostly manageable with supportive measures. In this heterogeneous patient group, a nonsignificant effect of pirfenidone treatment on pulmonary function was seen, underlining the need for more data on patient selection criteria and efficacy of pirfenidone, particularly in patients with coexistent emphysema and concomitant NAC/CCS treatment.
Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is ...known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF.
Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC).
We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (rs=-0.66), and directly with RV (rs=0.69) and RV/TLC (rs=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (rs=0.67, P<0.001).
Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF.
Cystic fibrosis (CF) is the most frequent inherited disorder leading to premature death in the Caucasian population. As life expectancy is limited by pulmonary complications, repeated imaging chest ...X-ray, multislice high-resolution computed tomography (MS-HRCT) is required in the follow-up. Magnetic resonance imaging (MRI) of the lung parenchyma is a promising new diagnostic tool. Its value for imaging lung changes caused by CF compared with CT is demonstrated. MRI performs well when compared with CT, which serves as the gold standard. Its lack in spatial resolution is obvious, but advantages in contrast and functional assessment compensate for this limitation. Thus, MRI is a reasonable alternative for imaging the CF lung and should be introduced as a radiation-free modality for follow-up studies in CF patients. For further evaluation of the impact of MRI, systematic studies comparing MRI and conventional imaging modalities are necessary. Furthermore, the value of the additional functional MRI (fMRI) information has to be studied, and a scoring system for the morphological and functional aspect of MRI has to be established.
As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. ...The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs.
We did a multicentre, open-label, comparative, randomised trial in 49 centres in Austria, France, Germany, and Italy. Eligible patients had cystic fibrosis, were older than 10 years, and had newly diagnosed diabetes. We used a central randomisation schedule derived from a Geigy random number table to assign patients 1:1 to receive insulin or repaglinide, stratified by sex and age (10-15 years or >15 years). The primary outcome was glycaemic control assessed by mean change in HbA
concentration from baseline after 24 months of treatment. Differences between groups were assessed by linear models. The primary and safety analyses were done in the modified intention-to-treat population (including patients who stopped treatment early because of lack of efficacy). This trial is registered with ClinicalTrials.gov, number NCT00662714.
We enrolled 34 patients in the repaglinide group and 41 in the insulin group, of whom 30 and 37, respectively, were included in the analyses. At 24 months, glycaemic control was similar in the repaglinide and insulin groups (mean change in HbA
concentration from baseline 0·2% SD 0·7%, 1·7 mmol/mol 8·1 mmol/mol with repaglinide vs -0·2% 1·3%, -2·7 mmol/mol, 14·5 mmol/mol with insulin; mean difference between groups -0·4%, (95% CI -1·1 to 0·2 -4·4 mmol/mol, -11·5 to 2·7, p=0·15). The most frequent adverse events were pulmonary events (43 40% of 107 in the repaglinide group and 60 45% of 133 in the insulin group), and the most frequent serious adverse events were pulmonary events leading to hospital admission (five 50% of ten and seven 54% of 13, respectively).
Repaglinide for glycaemic control in patients with cystic-fibrosis-related diabetes is as efficacious and safe as insulin.
Mukoviszidose eV, Vaincre la Mucoviscidose, ABCF Association, and Novo Nordisk.
Chronic inflammation and remodeling of the airways remain a hallmark of cystic fibrosis (CF). However, knowledge of the associated mucosal micro-anatomical changes is limited. We evaluated the ...potential of optical coherence tomography (OCT) for in vivo imaging of the upper airway mucosa in CF patients.
A flexible OCT probe was used for cross-sectional imaging of the nasal mucosa in 25 CF patients and 25 healthy controls.
OCT images showed mucosal details including epithelium, basement membrane, lamina propria with seromucinous glands, and underlying cartilaginous structures. Mean nasal mucosa and epithelial layer thickness were increased in CF compared to controls. In CF patients, antibiotic therapy was associated with reduced nasal mucosa thickening.
OCT detected mucosal changes associated with upper airway inflammation and response to antibiotic therapy in CF patients. OCT may be a useful tool for quantitative in vivo assessment of structural changes of the airway mucosa.
To evaluate the fully automatic quantification of airway dimensions on chest multidetector computed tomography (MDCT) performed in cystic fibrosis (CF) patients. Airflow indices including predicted ...forced expiratory volume in 1 second (FEV1%) were used to study the impact on regional lung function.
MDCT data of patients with CF (14 children and 23 adults) and of control patients (11 children and 22 adults) were used to compute total diameter (TD), lumen area (LA), and wall thickness (WT) using dedicated software. Pulmonary function testing including FEV1% was performed in parallel and correlated with MDCT parameters in a generation-based analysis.
TD was largely increased in CF patients (third-generation to fourth-generation airways in children, first to ninth in adults; P<0.05). LA remained unchanged, but WT was also larger in CF compared with controls (third generation to sixth generation in children, first to eleventh in adults; P<0.05). In adult CF patients significant negative correlations for TD, LA, and WT with FEV1% were found for intermediate airways (fifth to seventh generation; r=-0.7 to -0.9) but not in pediatric CF patients and controls.
Automatic airway analysis succeeded in quantifying specific pathologies such as airway dilatation and wall thickening in CF patients at different ages. Moreover, our results indicate a shift in main airflow resistance to intermediate airways in cases of chronic CF. The objective computational parameters TD, LA, and WT should be considered for assessment and follow-up of CF airway disease.
Background and Objective: The objective of this study was to develop a specific instrument for measuring health-related quality of life (HRQL) in patients receiving home mechanical ventilation (HMV).
...Methods: The Severe Respiratory Insufficiency (SRI) Questionnaire was developed and tested for its psychometric properties following a multicentric clinical trial including 226 patients receiving HMV (mean age 57.3±14.0 years).
Results: Forty-nine items passed the selection process and were allocated to seven subscales: Respiratory Complaints, Physical Functioning, Attendant Symptoms and Sleep, Social Relationships, Anxiety, Psychologic Well-Being, and Social Functioning. Cronbach's α was >0.7 in all subscales and >0.8 in four subscales indicating high internal consistency reliability. Construct validity was confirmed by factor analysis, indicating one summary scale that accounts for 59.8% of the variance. Concurrent validity was confirmed by correlating subscales of the SRI and the SF-36 (0.21<r<0.79). Item-scale correlations revealed a high item discriminant validity. In addition, different diagnostic groups could be discriminated by the SRI. Here, the overall best HRQL was measured in the following order: patients with kyphoscoliosis, miscellaneous disorders, neuromuscular diseases, post-tuberculosis, and chronic obstructive pulmonary disease (P<.05).
Conclusion: The SRI is a new multidimensional instrument with high psychometric properties designed to measure specific HRQL in patients with SRI receiving HMV.
As pulmonary complications are life limiting in patients with cystic fibrosis (CF), repeated chest imaging chest x-ray, computed tomography (CT) is needed for follow up. With the continuously rising ...life expectancy of CF patients, magnetic resonance imaging (MRI) as a radiation-free imaging modality might become more and more attractive. The goal of this study was to prospectively assess the value of MRI for evaluation of morphologic pulmonary CF-changes in comparison to established imaging modalities.
Thirty-one CF patients (19 female, 12 male; mean age 16.7 years) with stable lung disease were examined by MRI: HASTE, coronal/transversal (TR/TE/alpha/TA: infinite/28 ms/180 degrees /18 s), multi-detector computed tomography (MDCT) (30 patients): 120 kV, dose modulated mAs, and chest x-ray (21 patients). Image evaluation: random order, 4 chest radiologists in consensus; chest x-ray: modified Chrispin-Norman score; CT and MRI: modified Helbich score. The maximal attainable score for chest x-ray was 34, for MRI and CT 25. Median scores, Pearson correlation coefficients, Bland-Altman plots, and concordance of MRI to CT on a lobar and segmental basis were calculated.
The median MRI and MDCT scores were 13 (min 3, max 20) respectively 13.5 (min 0, max 20). The median chest x-ray score was 14 (min 5, max 32). Pearson correlation coefficients: MRI/CT = 0.80, P < 0.0001; MRI/chest x-ray = 0.63, P < 0.0018; chest x-ray/CT = 0.75, P < 0.0001. The median lobe related concordance was 80% for bronchiectasis, 77% for mucus plugging, 93%, for sacculation/abscesses, and 100% for collapse/consolidation.
Morphologic MRI of the lung in CF patients demonstrates comparable results to MDCT and chest x-ray. Because radiation exposure is an issue in CF patients, MRI might have the ability to be used as an appropriate alternative method for pulmonary imaging.
Abstract Background Chronic inflammation and remodeling of the airways remain a hallmark of cystic fibrosis (CF). However, knowledge of the associated mucosal micro-anatomical changes is limited. We ...evaluated the potential of optical coherence tomography (OCT) for in vivo imaging of the upper airway mucosa in CF patients. Methods A flexible OCT probe was used for cross-sectional imaging of the nasal mucosa in 25 CF patients and 25 healthy controls. Results OCT images showed mucosal details including epithelium, basement membrane, lamina propria with seromucinous glands, and underlying cartilaginous structures. Mean nasal mucosa and epithelial layer thickness were increased in CF compared to controls. In CF patients, antibiotic therapy was associated with reduced nasal mucosa thickening. Conclusions OCT detected mucosal changes associated with upper airway inflammation and response to antibiotic therapy in CF patients. OCT may be a useful tool for quantitative in vivo assessment of structural changes of the airway mucosa.
To collect benchmark data on the MOS 36-Item Short-Form Health Status Survey (SF-36) in patients receiving noninvasive positive pressure ventilation and to examine whether health-related quality of ...life is influenced by the underlying disease or by physical parameters.
Multicentric clinical cross-sectional trial in four general wards specialized in noninvasive positive pressure ventilation.
226 patients (78 chronic obstructive pulmonary disease, 57 kyphoscoliosis, 20 posttuberculosis sequelae, 17 Duchenne muscular dystrophy, 13 polyneuropathy, 13 myopathy, 6 amyotrophic lateral sclerosis, 12 obesity-hypoventilation syndrome, 4 poliomyelitis sequelae, 3 phrenic nerve lesion, 3 central hypoventilation syndrome) who used noninvasive positive pressure ventilation for home mechanical ventilation.
Health-related quality of life as assessed by the SF-36 was lower than in the general population. Overall the Physical Component Summary (PCS) was significantly lower than the general population norm; the Mental Component Summary (MCS) was also reduced but less markedly. Patients with chronic obstructive pulmonary disease were more impaired in MCS than those with kyphoscoliosis. PCS was significantly associated with age. Gender, lung function, and arterial blood gas values were not significant predictors of health-related quality of life.
Benchmark SF-36 data in patients receiving noninvasive positive pressure ventilation are given. Although physical health is significantly impaired in these patients, this does not necessarily lead to mental limitation, and mental health is influenced by the underlying disease, but not by physical parameters.
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