Optical coherence tomography detects structural abnormalities of the nasal mucosa in patients with cystic fibrosis.

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.

Pirfenidone in idiopathic pulmonary fibrosis: real-life experience from a German tertiary referral center for interstitial lung diseases.

BACKGROUND: 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. OBJECTIVES: To assess recent course of disease, adverse events and compliance in patients who started pirfenidone. METHODS: 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%. RESULTS: 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. CONCLUSIONS: 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.

Pulmonary emphysema in cystic fibrosis detected by densitometry on chest multidetector computed tomography.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Automatic airway analysis on multidetector computed tomography in cystic fibrosis: correlation with pulmonary function testing.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A 65-year-old man with an endobronchial gossypiboma after lobectomy for abscessing pneumonia.

We present a case of a 65-year-old man with recurrent hemoptysis and weight loss for 6 months. Thirty-two years earlier, lobectomy of the right lower lobe had been performed for abcessing pneumonia. Due to recurrent pulmonary infections after lobectomy the patient had to retire at the age of 46. A diagnostic procedure to explain the hemoptysis was performed. A computed tomogram revealed a suspicious formation in the bronchus intermedius, and the patient was referred to our department with the suspicion of lung cancer. During bronchoscopy an endobronchial mass was detected and extracted whole with a foreign-body forceps. Textile fibers of a sponge in the histology specimen led to the final diagnosis of gossypiboma (also known as textiloma). After removal of the gossypiboma no further pulmonary infections occurred.

A novel approach to CFTR mutation testing by pyrosequencing-based assay panels adapted to ethnicities.

BACKGROUND: Cystic fibrosis (CF) is a common autosomal recessive genetic disorder caused by a variety of sequence alterations in the CFTR gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)]. Because the relative prevalence of mutations strongly depends on the ethnic background, first-level testing of CF as defined by recent consensus recommendations ought to be adaptable to the ethnicity of patients. METHODS: We therefore developed and implemented a diagnostic approach to first-level testing for CF based on published mutation frequencies and Pyrosequencing (PSQ) technology that we complemented with standard procedures of mutation detection at the second level. RESULTS: The current test system of PSQ assays for 46 target CF mutations [including CFTRdele2,3 (21 kb) and 1342-6 (T)(n) (5T/7T/9T)] permits recombinations of single assays to optimize sensitivities for certain ethnicities. By easy expansion of the original mutation panel, the first-level test sensitivities with other ethnic groups would be increased, provided that the mutation frequencies are known. The test was validated with our local, ethnically mixed, but mainly German population (155 patients). The mutation-detection rate for the 92 patients whose CF was confirmed by the sweat test was 89.0% for the patients of German descent (73 of the 92 patients) and 73.7% for the patients of any other origin (19 of the 92 patients). Ethnicity-adapted testing panels for our foreign CF patients would increase the sensitivities for the respective groups by approximately 5%. CONCLUSIONS: PSQ-based genotyping is a reliable, convenient, highly flexible, and inexpensive alternative to conventional methods for first-level testing of CFTR, facilitating flexible adaptation of the analyzed mutation panel to any local ethnic group.

Assessment of morphological MRI for pulmonary changes in cystic fibrosis (CF) patients: comparison to thin-section CT and chest x-ray.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Proton MRI appearance of cystic fibrosis: comparison to CT.

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.

Assessment of hemodynamic changes in the systemic and pulmonary arterial circulation in patients with cystic fibrosis using phase-contrast MRI.

Cystic fibrosis (CF) leads to disabling lung disease and pulmonary hypertension (PH). The goal of this study was to assess the hemodynamics in the systemic and pulmonary arterial circulation of patients with CF using MRI. Ten patients with CF and 15 healthy volunteers were examined (1.5-T MRI). Phase-contrast flow measurements were assessed in the ascending aorta, pulmonary trunc, and the left and right pulmonary arteries (PA), resulting in the following parameters: peak velocity (PV) (centimeters per second) velocity rise gradient (VRG), time to PV (milliseconds), and the average area (centimeters squared). The blood flow ratio between the right and left lungs and the bronchosystemic shunt were calculated. For the ascending aorta and pulmonary trunc no parameter was significantly different between both populations. In the right PA a significantly lower PV (p=0.001) and VRG (p=0.02) was found. In the left PA there was a significantly (p=0.007) lower PV but no significant (p=0.07) difference between the VRG. The areas of the right (p=0.08) and left (p=0.5) PA were not significantly enlarged. For the volunteers a linear increase of PV in both PA was found with age, while it decreased in patients with CF. The blood flow distribution (right/left lung) showed no significant (p=0.7) difference between the groups. There was a significantly (p<0.001) higher bronchosystemic shunt volume in patients with CF (1.3 l/min) than in volunteers (0.1 l/min). Magnetic resonance based flow measurements in the right and left PA showed first indications for early development of PH. The significant increase in bronchosystemic shunt volume might be indicative fo the extent of parenchymal changes.

The Severe Respiratory Insufficiency (SRI) Questionnaire: a specific measure of health-related quality of life in patients receiving home mechanical ventilation.

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 alpha 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

Evaluation of health-related quality of life using the MOS 36-Item Short-Form Health Status Survey in patients receiving noninvasive positive pressure ventilation.

OBJECTIVE: 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. DESIGN AND SETTING: Multicentric clinical cross-sectional trial in four general wards specialized in noninvasive positive pressure ventilation. PATIENTS AND PARTICIPANTS: 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. MEASUREMENTS AND RESULTS: 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. CONCLUSIONS: 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.