Lung cancer in a CF patient: combination of bad luck or is there more to say?

Patients with cystic fibrosis have increased risk for gastrointestinal cancer, lymphoid leukemia and testicular carcinomas. Chronic inflammation does not seem to be the only contributing factor. Mutations and epigenetic alterations in the CFTR gene may alter susceptibility to develop cancer. Lung cancer is up to now not frequently observed in CF patients. In lung cancer patients without CF low CFTR expression is significantly associated with advanced staging, lymph node metastasis. As the management and life expectancy of patients with cystic fibrosis have improved substantially in recent years, we expect an increased number of these patients diagnosed with lung cancer. In addition, it is possible that they, as a result of CFTR-dysfunction, will present with more aggressive lung tumors. Treating cancer in CF patients is a challenge because of multi-organ involvement and chronic colonization by resistant pathogens. The effectiveness and safety of immunotherapy in this population needs to be further evaluated.

Pulmonary function changes following helical tomotherapy in patients with inoperable, locally advanced non-small cell lung cancer.

PURPOSE: To evaluate alterations in pulmonary function indices after helical tomotherapy and explore potential associations with biologically corrected dosimetric parameters. PATIENTS AND METHODS: In 64 patients with inoperable locally advanced non-small cell lung cancer, pulmonary function tests before and within 6 months after radiotherapy were evaluated retrospectively. In the case of concurrent chemotherapy a total dose of 67.2 Gy was delivered, otherwise 70.5 Gy was provided. In 44 patients, late pulmonary function changes (≥6 months after radiotherapy) could also be assessed. RESULTS: In the entire patient group, there were significant declines in forced expiratory volume in 1s (FEV1) (average change -4.1% predicted; P = 0.007), in forced vital capacity (FVC) (-4.9% predicted; P = 0.002), total lung capacity (TLC) (-5.8% predicted; P = 0.0016) and DLCO (diffusing capacity of the lung for carbon monoxide corrected for hemoglobin level) (-8.6% predicted; P < 0.001) during the first 6 months. Corresponding FEV1, FVC, TLC and DLCO declines in the subgroup with late measurements (after 11.3 months on average) were -5.7, -7.4, -7.0, -9.8% predicted. A multivariate analysis including V5 Gy, V10 Gy, V20 Gy, V40 Gy, V60 Gy, mean lung dose (MLD), gross tumor volume (GTV) and planning target volume (PTV) as potential covariates showed that GTV was the most consistent contributor, being significant for ∆FEV1 (P = 0.003), ∆FVC (P = 0.003), ∆TLC (P = 0.001) and ∆DLCO (P = 0.01). V5 Gy or V10 Gy did not contribute to any of the lung function changes. CONCLUSIONS: The decline in pulmonary function indices after helical tomotherapy was of similar magnitude to that observed in studies reporting the effect of conformal radiotherapy on lung function. Diffusion capacity was the parameter showing the largest decrease following radiation therapy as compared to baseline and correlated with gross tumor volume. None of the alterations in pulmonary function tests were associated with the lung volume receiving low-dose radiation.

Emergence of livestock-associated MRSA isolated from cystic fibrosis patients: Result of a Belgian national survey.

BACKGROUND: This study aims to determine the prevalence and characteristics of Staphylococcus aureus in Belgian cystic fibrosis (CF) patients. METHODS: Non-duplicate respiratory samples from 510 CF-patients (2012-2013) were examined. One isolate per patient was analysed unless different phenotypes were recovered. Isolates were investigated for mecA/mecC, toxins presence, spa-typing, MLST and SCCmec-typing. Potential livestock-associated (LA) isolates were examined for their immune-evasion-cluster (IEC) genes. RESULTS: S. aureus (n = 380), including 41 small-colony variants (SCVs), were isolated from 66.7% patients. The prevalence of methicillin-resistant S. aureus (MRSA) colonization was 4.9%. Two MRSA isolates carried toxic shock syndrome toxin 1 (TSST-1). Most MRSA (65%) belonged to two nosocomial epidemic clones (CC5, CC8) widespread in Belgium. Methicillin susceptible S. aureus (MSSA) showed great genetic diversity. Five of 33 isolates belonging to potential LA-lineages were IEC negative, including three methicillin-resistant isolates, suggesting an animal origin. CONCLUSIONS: The MRSA-prevalence in Belgian CF-patients remained constant (2001-2013), but SCV-prevalence increased. Most MRSA belonged to health-care-associated clones. Three patients carrying LA-MRSA were found, requiring further investigation to determine the risk factors for LA-MRSA acquisition.

Increase in ventilated air spaces after eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients.

Effective microbiogical eradication of methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) can be obtained, but its effect is not always clear-cut in terms of spirometric indices. The aim of this observational prospective cohort study was to study the potential effect of eradication of chronic MRSA infection on lung function including ventilation distribution. Six CF patients, chronically colonized with MRSA (median age: 21 years (range 14-46); median FEV1: 76 (95%CI 58-98)%pred) were successfully eradicated using oral rifampicin and fusidic acid in combination with topical decolonization measures. Lung function and multiple breath washout test were performed at the start and at the end of the eradication protocol and after an average follow-up period of 7·5±1·5(SD) months. One patient cultured MRSA again 4 months after successful eradication. All patients reported reduced sputum production and viscosity. By the end of the follow-up period, there was an increase in ventilated FRCMBW and no change in plethysmographic FRCPL. This resulted in a significant decrease of trapped air by half a litre (from 579 to 40 ml; P = 0·013). Lung clearance index (LCI) also showed a small but significant decrease (from 7·2 to 6·7; P = 0·014) after eradication of MRSA. We conclude that MRSA eradication can be successful, also in terms of recruitment of previously unventilated air spaces, potentially due to reduced sputum production and/or viscosity.

An incident case of primary acquired pulmonary alveolar proteinosis.

This is a case of a primary acquired pulmonary alveolar proteinosis (PAP) in an asymptomatic patient, on the waiting list for kidney transplantation, confirmed on lung biopsy and by identifying anti-GM-CSF antibodies.

Whole-lung lavage: a successful treatment for restoring acinar ventilation distribution in primary acquired pulmonary alveolar proteinosis.

A 51-year-old active smoker with primary acquired pulmonary alveolar proteinosis (PAP) diagnosed by biopsy and anti-GM-CSF antibodies was treated safely with whole-lung lavage (WLL). This resulted in a rapid improvement of symptoms and arterial blood oxygenation, but not of standard lung function parameters. However, we also performed the multiple-breath nitrogen washout (MBW) test to determine the lung clearance index (LCI) as well as indices of acinar ventilation heterogeneity (S(acin)) and conductive ventilation heterogeneity (S(cond)). At baseline, a distinct abnormality was seen for S(acin) and LCI, while S(cond) was at the upper limit of normal for this subject. S(acin), in particular, was in excess of the S(acin) abnormality corresponding to a 20-pack-year smoking history. Immediately after WLL, S(acin) and S(cond) both fell to within a normal range while LCI also decreased but remained abnormal. The S(acin) decrease was much greater than the S(cond) decrease, which was to be expected after 1 week of smoking cessation at the hospital (smoking was resumed after release from hospital). A follow-up visit 7 weeks after WLL revealed a spectacular improvement on CT scan and improvements in standard lung function. Another follow-up visit 14 weeks after WLL showed further improvements in standard lung function, and both S(acin) and S(cond) remained well within the normal range, and LCI was above the upper limit of normal. We conclude that in this patient, removal of excess surfactant by WLL resulted in a restored ventilation distribution in most of the distal air spaces.

Prevalence and impact on FEV(1) decline of chronic methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with cystic fibrosis. A single-center, case control study of 165 patients.

BACKGROUND: Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in Cystic Fibrosis (CF) and the impact on CF disease progression are still under debate. The objectives of this study were to determine clinical variables associated with MRSA colonization and examine impact on FEV(1) evolution in CF patients. METHODS: A retrospective case-control study using the University Hospital of Brussels CF clinic patient registry from 2002 to 2010, comparing clinical variables and decline of FEV(1) of MRSA positive patients with age and sex matched controls, chronically colonized with S. aureus. RESULTS: Thirty of the 165 CF patients, chronically colonized with S. aureus, had cultures positive for MRSA (18.2%). Excluding patients under 4 years, the prevalence became 15.2% (23/151). Chronic colonization (i.e., three or more consecutive positive cultures) was found in 19/151 (12.6%). The MRSA positive group showed a higher proportion of patients with genotype F508del, less pancreas sufficient patients, more bronchiectasis and more frequent hospitalization. The FEV(1) recorded one year prior to, and at the moment of MRSA acquisition, was lower but not significantly different from that obtained in controls (72.9%±26.6 vs 84.3±21.8 and 68.2%±27.1 vs 81.4%±24.3 respectively, p>0.1). However, FEV(1) decline over 2- and 6-year periods, were significantly greater in the chronic MRSA group than in the controls (-5%±5.5 vs -2.5±2.3 over 2 years (p=0.043) and -1.8%±4.6 vs -1.0%±1.9 over a 6-year period (p=0.026)). CONCLUSION: In our center the prevalence of MRSA in CF patients, chronically colonized with S. aureus and over the age of 4 years, was 15.2% (12.6% chronic infection). MRSA colonization was shown to be associated with a genotype F508del, presence of bronchiectasis and hospitalization. Our spirometric data also show that a MRSA episode entails an FEV(1) decline that is almost double that predicted for CF patients who can remain unaffected by MRSA.