Glycemic control and FEV1 recovery during pulmonary exacerbations in pediatric cystic fibrosis-related diabetes

RationaleWhether short-term glucose control in cystic fibrosis-related diabetes (CFRD) is associated with FEV₁ recovery during acute pulmonary exacerbations is unclear.MethodsData from all patients with CFRD ages 6–21 years hospitalized in 2010–2016 for pulmonary exacerbations at our CF Center were analyzed, including CFRD status at each encounter, all FEV₁ recorded during each exacerbation, and relevant clinical covariates. Glucose control was analyzed using meter blood glucose area under the curve (AUC) indices. The primary outcome was FEV₁ recovery.ResultsPatients with CFRD who finished IV antibiotics at home were treated for longer than those fully treated in the hospital (22.2 vs. 13.8 days). In those who finished treatment at home, poor inpatient glycemic control was associated with lower lung function improvement: when comparing the 75th to the 25th percentile of each glycemic index (i.e., “poorer” vs. “better” glycemic control), FEV₁ recovery at discharge was 20.1% lower for glucose AUC (95%CI −0.4%, −39.9%); 20.9% lower for 48-h AUC (95%CI −2.7%, −39.1%); and 28.2% lower for AUC/day (95%CI −7.1%, −49.3%). Similar results were found at the end of IV antibiotics and at clinic follow-up. Likewise, patients with poor glycemic control had a lower slope of inpatient FEV₁ recovery. Analysis in patients with normal glucose tolerance was largely non-significant. No associations were found between hemoglobin A1c and FEV₁ recovery.ConclusionsIn patients with CFRD who complete IV antibiotic treatment at home, poor inpatient glycemic control is associated with worse FEV₁ recovery despite longer duration of treatment.     

Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis

BACKGROUND—The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: "Are inhaled corticosteroids able to slow down the decline in lung function (FEV₁) in COPD?"METHODS—A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with "asthmatic features" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 µg beclomethasone daily, six with 1600 µg budesonide daily, and eight with 800 µg beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV₁ was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.RESULTS—No baseline differences were observed (mean age 61 years, mean FEV₁ 45% predicted). The estimated two year difference in prebronchodilator FEV₁ was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV₁ showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.CONCLUSIONS—This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV₁ during two years of treatment with relatively high daily dosages of inhaled corticosteroids.     

Smoking, Lung Function and the Prognosis of Abdominal Aortic Aneurysm

Background the UK Small Aneurysm Trial was established to test the benefit of prophylactic elective surgery for small abdominal aortic aneurysms (4.0–5.5 cm in diameter) and identify prognostic risk factors, including smoking. Patients, methods and outcomes one thousand and ninety patients (902 men and 188 women, mean age 69.3 years) were randomised to either early elective surgery or ultrasonography surveillance until the aneurysm diameter exceeded 5.5 cm, mean follow-up was 4.6 years. Baseline assessments included lung function tests and cotinine (a smoking marker). The principal outcome measures were all-cause mortality and aneurysm rupture. Results during the course of the trial, aneurysm rupture was diagnosed in 25 patients and 309 patients died. Whereas self-reported smoking status was not significantly associated with survival, patients without any trace of plasma cotinine had a significantly improved long-term (6-year) survival,p =0.02. Current smokers had a lower FEV₁than past- and never-smokers. FEV₁was the most powerful predictor of long-term (6-year) survival, the crude death rates per 100 person-years were 9.1, 6.9 and 4.6 for those with FEV₁<1.9 l, 1.9–2.5 l and >2.5 l respectively, p=0.001. Moreover, the rupture rate was 1.9% per year for patients positive for plasma cotinine compared with 0.5% in those without trace of plasma cotinine,p =0.004. Conclusions self-reported smoking status underestimates the effect of continued smoking on the prognosis of patients with small abdominal aortic aneurysm. Patients with high plasma cotinine concentrations (smokers) have an increased risk of aneurysm rupture and poorer long-term survival.     

Standardized Treatment of Pulmonary Exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary Exacerbations

Background

Pulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx.

The effect of antibiotic changes during treatment of cystic fibrosis pulmonary exacerbations

BackgroundAntibiotics are often changed during treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) who have a poor clinical response. We aimed to characterize the reasons CF providers change antibiotics and examined the effects of antibiotic changes on lung function recovery.MethodsThis was a retrospective cohort study using the Toronto CF Database from 2009 to 2015 of adults and children with CF PEx treated with intravenous antibiotics. The co-primary outcome measure was absolute and relative change in forced expiratory lung volume in 1 s (FEV₁) at end of treatment and follow-up. Secondary outcome assessed the proportion of patients returning to > 90% or > 100% previous baseline FEV₁.ResultsA total of 399 PEx were included of which 105 had antibiotic changes. Reasons for antibiotic changes included change in antibiotic route prior to discharge (26%), drug reactions (20%), poor FEV₁ response (25%), targeting additional microbes (16%) and lack of symptom improvement (13%). In our multivariable analysis, among non-responders (< 90% FEV₁ recovery to baseline or lack of symptom improvement at the interim time point), a change in antibiotics was not associated with any significant difference in absolute or relative FEV₁ at end of treatment or at follow-up. Antibiotic change in non-responders was not associated with improved return to 90% or 100% baseline FEV₁ at end of treatment or follow-up.ConclusionsChanging antibiotics during CF PEx treatment in those with poor clinical response was not associated with any improved FEV₁ response or return to baseline lung function.     

Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: Comparing hospital and home care

BACKGROUND: A cost-effectiveness evaluation comparing home-based and hospital-based treatment with intravenous antibiotics for respiratory exacerbations in adults with cystic fibrosis (CF) has not been previously undertaken. METHODS: The study was conducted in a UK adult CF centre from a health service perspective. Clinical outcome and resource use data were obtained from a retrospective one-year study and combined with unit cost data in an incremental economic analysis. The primary outcome measure was percentage change in FEV(1); "effectiveness" was defined as maintenance of baseline average FEV(1) over the one-year study period. RESULTS: 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year, there had been a mean percentage decline in FEV(1) compared with baseline average for home-treated patients but an improvement for hospital-treated patients (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). Treatment was deemed "effective" in more hospital (58.8%) than home (42.6%) patients. The cost of hospital treatment was higher than home treatment (mean difference 9,005 pounds, 95% CI 3,507 to 14,700, p<0.001). The mean ICER was 46,098 pounds (2.5th and 97.5th percentiles -374,044 and 362,472). CONCLUSIONS: Hospital treatment was more effective but more expensive than home treatment. Potential methods to improve outcome at home should be considered but these may have resource implications.     

Temocillin in cystic fibrosis: A retrospective pilot study

BackgroundTemocillin is currently used in the treatment of acute pulmonary exacerbations caused by Burkholderia cepacia complex and multi-resistant Pseudomonas aeruginosa in cystic fibrosis (CF) patients despite little published clinical data. This study assessed if intravenous (IV) antibiotic therapy including temocillin was equivalent to standard combination therapy for an acute exacerbation.MethodsA retrospective, pilot cross-over study. Adult patients attending two CF centres between 1997 and 2006 who had received a course of IV antibiotics including temocillin (TIV) and a further IV course (within ± 1 year) which did not include temocillin (NTIV) were included. Outcome measures at the start and end of each IV course were recorded (FEV₁%, FVC%).ResultsTwenty six patients had received temocillin. Baseline values of FEV₁% predicted were comparable for both groups (TIV: 37(18%), NTIV: 39(20%)). FEV₁% increased by 7.12(11.67)% after TIV (p < 0.01) and 6.65(7.62)% after NTIV (p < 0.01). There was no significant difference between the IV courses in mean %change in lung function TIV versus NTIV (FEV₁ 0.46% [95%CI: − 4.55 to 5.48%]).ConclusionThese data suggest equivalence in the lung function outcome of IV antibiotic therapy includingtemocillin versus standard IV antibiotic therapy.     

Lung function tests and a `vertical'' P wave axis in the electrocardiogram

Chapman, T. T. (1974).Thorax, 29, 106-109. Lung function tests and a `vertical' P wave axis in the electrocardiogram. The relationship between a vertical P wave axis and impaired lung function was studied in 1,144 patients with chronic non-specific lung disease. There was a significant relationship between a vertical P wave axis and reduction in forced expiratory volume (FEV₁), FEV₁ as a percentage of vital capacity (FEV₁%VC), residual volume (RV), and transfer factor (TF); this relationship was closest in the case of the FEV₁%VC. There was no significant correlation between P wave axis and the forced inspiratory volume (FIV₁).     

Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis

Background

Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols.

Poor recovery from a pulmonary exacerbation does not lead to accelerated FEV1 decline

Background

Patients with CF treated for pulmonary exacerbations (PEx) may experience faster subsequent declines in FEV₁. Additionally, incomplete recovery to baseline FEV₁ occurs frequently following PEx treatment. Whether accelerated declines in FEV₁ are preceded by poor PEx recovery has not been studied.

A retrospective analysis of the impact of azithromycin maintenance therapy on adults attending a UK cystic fibrosis clinic

BackgroundAzithromycin is widely used as an immunomodulatory agent in the treatment of cystic fibrosis with previous literature documenting improvements in lung function and a reduction in infective exacerbations. The maximal study period in adults has been six months.Methods81 adult patients taking continuous azithromycin were retrospectively identified. Percentage predicted FEV₁ and courses of intravenous antibiotics were examined at yearly intervals two years prior to and two years after azithromycin initiation.ResultsFEV₁ deteriorated in the two years before starting azithromycin by a mean of 2.02% per year. In the year following initiation, FEV₁ increased by 1.15% (P = 0.01). However, a mean 2.58% reduction was observed in year two. There was no statistically significant effect on courses of intravenous antibiotics.ConclusionsAzithromycin resulted in an improved FEV₁ at year one. This effect was not sustained beyond the first year of treatment.     

Die geriatrische Frührehabilitation nach hüftgelenknahem Oberschenkelbruch

Background

Modern strategies for postoperative care of patients with hip fractures include early discharge from the acute care hospital to inpatient interdisciplinary rehabilitation facilities. Whether these programs are effective for the patients and improve their long-term outcomes or if they simply transfer costs, with a reduction of the inpatient days in the acute care hospital, is currently under discussion.

Patients and methods

This prospective study included 282 patients with hip fracture admitted to our trauma center were included into the prospective study. The mean patient age was 86±8 (65–110) years. All patients were treated operatively. After a mean of 12±9 days, the patients underwent inpatient interdisciplinary geriatric rehabilitation for a mean of 27±13 (4–103) days. The primary outcome measure was their activities of daily living (Barthel index) before, at the end of rehabilitation, and 1 year after trauma. In addition, patient-related variables were correlated with the Barthel index.

Results

With discharge from the acute care hospital, the Barthel index was 42±20 points and it increased during rehabilitation to 65±26 points. One year later the Barthel index was 67±28 points. Ninety percent of patients improved their Barthel index during rehabilitation. Within 1 year, 40% of patients deteriorated in their activities of daily living. Fifty one percent of patients were reintegrated back to their homes. Patients who lived at home before trauma and were reintegrated back to their homes had a significant higher Barthel index (75±24) 1 year after trauma than patients who were living in a nursing care facility before the trauma (Barthel index 52±27). The variables of age, level of cognition, and type of fracture had no influence on the long-term outcome. An extension of rehabilitation above the mean time period did not improve the sustainable clinical outcome.

Conclusion

Postoperative inpatient rehabilitation programs enhance short-term activities of daily living. In particular, patients who lived at home before the trauma and were reintegrated back home benefited in perpetuity from geriatric rehabilitation. A policy for early discharge to geriatric rehabilitation is associated with extension of overall hospital stay. This association along with the related increased health care costs should be weighed against the sociofunctional effectiveness of these programs.     

Prediction of pulmonary function after lobectomy

Aim-Background

Lung cancer is the most common cause of cancer death in both men and women in our country. It has been estimated that there will be 7,000 lung cancer deaths every year in Greece. However, many patients with bronchogenic carcinoma also have coexistent obstructive lung disease. In these patients, preoperative prediction of functional status after lung resection is mandatory. The aim of our study was to determine the effect of lobectomy on postoperative spirometric lung function.

Methods

Seventy-two patients underwent spirometric pulmonary tests preoperatively, and at three and six months after surgery. The predicted postoperative forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁) were calculated using the following formula suggested by Juhl and Frost.

Results

The functional percentage loss at six months for lobectomies was 7.34% for FVC and 7.72% for FEV₁ respectively. The linear regression analysis derived from the correlation between predicted and measured FEV₁ revealed the following equation: FEV ₁ POSTOP = 0.00211+0.896660 X FEV ₁ PREOP.

Conclusions

We conclude that our formula is a reliable method for predicting postoperative respiratory function of the patients with lung cancer.     

Clinical impact of levofloxacin inhalation solution in cystic fibrosis patients in a real-world setting

BackgroundLevofloxacin inhalation solution is the most recently approved inhaled antibiotic in Europe and Canada for adult cystic fibrosis patients. Its efficacy and safety have been assessed in randomized controlled trials. Our aim was to evaluate real life experience and outcomes in our treatment centre.MethodsWe evaluated the efficacy of inhaled levofloxacin solution in 86 patients with cystic fibrosis in terms of the following outcome parameters: changes in %-predicted forced expiratory volume in one second (FEV₁), body-mass index (BMI), and exacerbation rate. We conducted an intraindividual analysis of patients who received levofloxacin inhalation solution twice daily 240 mg for at least 4 weeks.ResultsChange in FEV₁% predicted for the treatment period was +2.27% (p=0.0027) after 4 weeks. There was no change in BMI for overall group, but exacerbation rate compared to one year before initiation of inhaled levofloxacin decreased significantly (p=0.0024) after 1 year of treatment (3.23 ± 1.39 versus 2.71 ± 1.58).ConclusionsIn patients with cystic fibrosis, inhaled levofloxacin solution has the potential to improve FEV₁ and to reduce the number of bronchopulmonary exacerbations.     

Natural history of abdominal aortic aneurysm with and without coexisting chronic obstructive pulmonary disease

Purpose:To study the relation between abdominal aortic aneurysms and chronical obstructive pulmonary disease (COPD), in particular the suggested common elastin degradation caused by elastase and smoking. Methods:A cross-sectional population study and a prospective cohort study of small abdominal aortic aneurysms was performed in a community setting. All previous diagnoses recorded in a hospital computer database were received for 4404 men 65 to 73 years of age who had been invited to a population screening for abdominal aortic aneurysm. One hundred forty-one men had AAA (4.2%). They were asked to participate in an interview, a clinical examination, and collection of blood sample. Men with an abdominal aortic aneurysm 3 to 5 cm in diameter were offered annual ultrasound scans to check for expansion. Results:Among patients with COPD 7.7% had abdominal aortic aneurysms (crude odds ratio = 2.05). The adjusted odds ratio, however, was only 1.59 after adjustment for coexisting diseases associated with abdominal aortic aneurysm (P = .13). The mean annual expansion was 2.74 mm per year among patients with COPD, 2.72 among patients without COPD, and 4.7 mm among patients who used oral steroids compared with 2.6 among patients who did not use steroids (P < .05). Concentration of serum elastin peptide and plasma elastase–α₁-antitrypsin complexes correlated negatively with forced expiratory volume in the first second (FEV₁) among patients with COPD. However, multivariate regression analysis showed that concentration of serum elastin peptide, therapy with β-agonists, and FEV₁ correlated positively with degree of expansion but that concentration of plasma elastase–α₁-antitrypsin complexes and serum α₁-antitrypsin did not influence expansion, suggesting that elastase plays an important role in the pathogenesis of COPD but not of abdominal aortic aneurysm. Conclusion:The high prevalence of abdominal aortic aneurysm among patients with COPD is more likely to be caused by medication and coexisting diseases rather than a common pathway of pathogenesis. (J Vasc Surg 1998;28:226-33.)     

A retrospective 12-month study of conversion to everolimus in lung transplant recipients

Background

Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation.

Methods

We retrospectively assessed the 12-month outcomes of the conversion to everolimus among lung recipients in six Spanish centers.

Results

From March 2005 to December 2007, 65 lung recipients who were at a mean posttransplantation time of 10.2 ± 7.9 months were converted to everolimus, mainly because of BOS (64.6%) or renal insufficiency (RI; 12.3%). The initial dose of everolimus was 1.9 ± 0.6 mg/d and the mean blood trough levels were stable over time (6.4 ± 2.8 ng/mL at 12 months). Conversion to everolimus allowed us to eliminate the calcineurin inhibitor (CNI) in 21% of patients. Among the overall population, the forced expiratory volume at 1 second (FEV₁) and renal function remained stable. Mean FEV₁ did not change among the 35 (81%) patients surviving BOS at 12 months: preconversion FEV₁: 1.449.5 ± 641.9 mL vs 12-month FEV₁: 1420.0 ± 734.6 mL (P = .866). There was a significant improvement in renal function among the RI patients with mean glomerular filtration rates of 42.2 ± 15.2 mL/min/1.73 m² (P = .043) at 6 and 44.4 ± 18.8 mL/min/1.73 m² at 12 months, (P = .063) and a decrease in the use of CNIs from 1% of RI patients preconversion to 57% at 6 and 75% at 12 months. With a mean of 8.1- months follow-up (range: 1–31.3) overall survival was 84.6% at 1 year and 50% at 22.3 months. Progressive BOS was the main cause of death. Reasons for everolimus discontinuation were patient death (n = 10), lack of efficacy (n = 4), gastrointestinal adverse events (n = 2), and edema (n = 2).

Conclusions

BOS and RI were the main indications for conversion to everolimus among lung recipients. Conversion to everolimus improved renal function among patients converted because of RI. The present results were inconclusive regarding effects of everolimus on BOS.     

Standardized Treatment of Pulmonary Exacerbations (STOP) study: Observations at the initiation of intravenous antibiotics for cystic fibrosis pulmonary exacerbations

Background

The Standardized Treatment of Pulmonary Exacerbations (STOP) program has the intent of defining best practices in the treatment of pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF). The objective of this analysis was to describe the clinical presentations of patients admitted for intravenous (IV) antibiotics and enrolled in a prospective observational PEx study as well as to understand physician treatment goals at the start of the intervention.

Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries

BackgroundIvacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years.MethodsData from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity.ResultsUS analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5 years from year 1 of market availability (2012–2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV₁, −0.7 percentage points with ivacaftor vs −8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4 kg/m² with ivacaftor vs +1.6 kg/m² in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5 years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings.ConclusionsThis observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor.     

Clinical effect of lumacaftor/ivacaftor in F508del homozygous CF patients with FEV1 ≥ 90% predicted at baseline

ObjectiveThe first available CFTR modulator combination for homozygous F508del patients, lumacaftor/ivacaftor, has not been tested in patients with percentage predicted (pp)FEV₁ > 90 in the phase III trials. The objective of this study is to share real life experience about treatment results in this group.MethodsIn this retrospective observational study, patients aged 6 years or older starting on lumacaftor/ivacaftor in standard care were in strict follow up. For these patients, data were obtained about FEV₁, BMI, CFQ-R and sweat chloride before start and after 6 months of treatment, and data about FEV₁ and BMI were recorded every 3 months. Exacerbations were recorded continuously.ResultsWe identified 40 patients with a ppFEV₁ ≥ 90 at the start of lumacaftor/ivacaftor who had been in follow up for at least 12 months. After 12 months, ppFEV₁ was unchanged, whereas mean absolute change in BMI was +0.88 (p = 0.001) with a mean change in SDS for BMI of +0.26 (p = 0.014). Mean CFQ-R overall score at 6 months improved by 2.6% (p = 0.004) and mean decrease in sweat chloride was -27.3 mEq/L (p = 0.000). Exacerbation rate declined from 1.03 to 0.53/person/year (p = 0.003). One patient discontinued treatment in the first 12 months because of progression of CFRLD, two paused treatment but resumed later.ConclusionHomozygous F508del patients starting lumacaftor/ivacaftor at ppFEV₁ ≥ 90 improved significantly in nutritional status, sweat chloride levels and exacerbation rate, but did not respond in ppFEV₁. Treatment is well tolerated in this patient group. These effects make it worth considering to treat this group of patients with lumacaftor/ivacaftor.     

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.