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We hypothesized that in patients with chronic obstructive pulmonary disease, loss of fat-free mass (FFM) and loss of bone mineral density (BMD) were related to (1) each other and may be clinically inapparent, (2) urinary markers of cellular and bone collagen protein breakdown, and (3) severity of lung disease. Eight-one patients and 38 healthy subjects underwent dual-energy X-ray absorptiometry to determine body composition and BMD. Urinary protein breakdown markers, inflammatory mediators, and their soluble receptors were determined. Thirty-three patients had a low fat-free mass index (kg/m2), 17 of whom had a normal body mass index. Thirty-two percent of patients (13% of healthy subjects) had osteoporosis at the hip or lumbar spine. The marker of cellular protein breakdown was elevated in patients and related to lung disease severity and body composition. The marker of bone collagen breakdown was greater in patients with osteoporosis. Inflammatory mediators were elevated in patients. Loss of FFM and loss of BMD were related, occurred commonly, and could be subclinical in patients with chronic obstructive pulmonary disease. Loss of both was greatest with severe lung disease. Increased excretion of cellular and bone collagen protein breakdown products in those with low FFM and BMD indicates a protein catabolic state in these patients. [ABSTRACT FROM AUTHOR]

Background: Transoral robotic surgery (TORS) or transoral laser microsurgery (TLM) offer excellent oncological outcomes for oropharyngeal squamous cell carcinoma caused by human papillomavirus (HPV) infection. TORS may offer greater margin clearance around tumors than TLM., Objective: To determine whether the differing energy sources used and surgical technique of TORS or TLM is associated with postoperative early swallowing function, feeding tube use, and specific factors related to quality of life., Design, Setting, and Participants: This prespecified cohort study was performed within the Postoperative Adjuvant Treatment for HPV-Positive Tumours (PATHOS) randomized clinical trial at 40 centers in the UK, Germany, France, the US, and Australia between November 1, 2015, and August 31, 2023. PATHOS trial participants with HPV-positive oropharyngeal carcinoma of stages T1 to T3 and N0 to N2b M0 (TNM7) who underwent TLM or TORS were eligible. Of 989 consecutively recruited patients on the PATHOS trial, 508 were eligible for this substudy., Exposures: The exposure of interest was TORS or TLM., Main Outcomes and Measures: Preplanned outcome measures included nasogastric tube insertion rates within 4 weeks after surgery, length of in-hospital stay following surgery, specific scales from the MD Anderson Dysphagia Inventory (MDADI), 35-item European Organization for Research and Treatment of Cancer Head and Neck Questionnaire (H&N35), and 30-item Quality of Life Questionnaire (QLQ C30), water swallow test results, and videofluoroscopy scores., Results: Of the 508 patients included in the analysis (390 [76.8%] male; median age, 58.3 [IQR, 52.8-63.6] years), 195 had TLM and 313 had TORS. Nasogastric tube insertion rates were higher after TORS than TLM (85 of 189 [45.0%] vs 10 of 126 [7.9%]; adjusted odds ratio [OR], 4.41 [95% CI, 1.01-19.32]). Mean scores favored TLM with small effect sizes in all MDADI domains and the H&N35 swallowing item at 4 weeks after surgery; between-group difference for the MDADI composite score was -4.89 (95% CI, -8.27 to -1.50); for the MDADI physical functioning score, -6.37 (95% CI, -10.15 to -2.59); for the MDADI global score, -10.02 (95% CI, -16.50 to -3.54); and for H&N35 swallowing score, 7.24 (95% CI, 2.17-12.30). No other measures showed evidence of clinically meaningful differences., Conclusions and Relevance: In this cohort study, functional outcomes were moderately less impaired 4 weeks following TLM compared with TORS. Once the longer-term outcomes for these patients are known, these findings could aid the design and use of future head and neck-specific surgical robots., Trial Registration: ClinicalTrials.gov Identifier: NCT02215265.

Objectives: This qualitative study explored patients' experiences and perceptions of the SCOPE2 trial. SCOPE2 examined radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemoradiotherapy (dCRT)., Setting: Recruitment at five clinical sites in England and Wales, UK., Participants: SCOPE2 trial participants were invited to take part in interviews from across five clinical sites. Participants self-selected to take part in up to three interviews across four different time points: baseline (before treatment) and at 2-3 months, 3-6 months or 6 months+ after baseline. There were five female and five male interview participants., Interventions: Participants were randomised to standard dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine, or an escalated dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine., Methods: This qualitative study used semistructured longitudinal interviews to explore the impact of treatment on patient outlook and quality of life and the impact of the COVID-19 pandemic. Interview data were thematically analysed., Results: 10 patients participated in 16 longitudinal interviews. Three participants were accompanied by companions. Participants experienced side-effects from radiotherapy and chemotherapy including nausea, throat pain, difficulties eating and regaining appetite, thrombosis and fatigue, although most of these symptoms gradually improved. Participants required more ongoing information and support regarding treatment side-effects and cancer status in order to improve their overall quality of life. Best practice examples involved key contacts providing practical advice and signposting support., Conclusion: Participants of the SCOPE2 trial reported short and longer-term side-effects from chemoradiotherapy, but these usually lessened over time. Participants attempted to be positive about their survival prospects by readjusting their expectations, priorities and lifestyles. Providing patients with ongoing opportunities to discuss detailed and timely information regarding treatment side-effects, aftercare and cancer status could improve the overall health and well-being of patients during oesophageal cancer trials and pathways., Trial Registration Number: NCT02741856; ISRCTN: 97125464., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain., Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of 18 F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m 2 )/capecitabine (625 mg/m 2 days 1-21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUV max ) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m 2 ) for a further induction cycle, then concurrently with radiotherapy over 25 fractions. Responders continued cis/cap for the duration of treatment. All patients (including responders) were randomised to standard (50Gy) or high (60Gy) dose radiation as part of the main study. Primary endpoint for the substudy was treatment failure-free survival (TFFS) at week 24. The trial was registered with International Standard Randomized Controlled Trial Number 97125464 and ClinicalTrials.govNCT02741856., Findings: This substudy was closed on 1st August 2021 by the Independent Data Monitoring Committee on the grounds of futility and possible harm. To this point from 22nd November 2016, 103 patients from 16 UK centres had participated in the PET-CT substudy; 63 (61.2%; 52/83 OSCC, 11/20 OAC) of whom were non-responders. Of these, 31 were randomised to car/pac and 32 to remain on cis/cap. All patients were followed up until at least 24 weeks, at which point in OSCC both TFFS (25/27 (92.6%) vs 17/25 (68%); p = 0.028) and overall survival (42.5 vs. 20.4 months, adjusted HR 0.36; p = 0.018) favoured cis/cap over car/pac. There was a trend towards worse survival in OSCC + OAC cis/cap responders (33.6 months; 95%CI 23.1-nr) vs. non-responders (42.5 (95%CI 27.0-nr) months; HR = 1.43; 95%CI 0.67-3.08; p = 0.35)., Interpretation: In OSCC, early metabolic response assessment is not prognostic for TFFS or overall survival and should not be used to personalise systemic therapy in patients receiving dCRT., Funding: Cancer Research UK., Competing Interests: SM declares research funding from Celgene. TM declares consulting fees from AstraZeneca and Teysuno; reports participation fees from Pierre Fabre and Pfizer; and has a role at Perspectum. All other authors declare that they have no relevant conflicts of interest., (© 2023 The Author(s).)

This article reviews progress over the past three decades related to the role of dendrimer-based, branch cell symmetry in the development of advanced drug delivery systems, aqueous based compatibilizers/solubilizers/excipients and nano-metal cluster catalysts. Historically, it begins with early unreported work by the Tomalia Group (i.e., The Dow Chemical Co.) revealing that all known dendrimer family types may be divided into two major symmetry categories; namely: Category I: symmetrical branch cell dendrimers (e.g., Tomalia, Vögtle, Newkome-type dendrimers) possessing interior hollowness/porosity and Category II: asymmetrical branch cell dendrimers (e.g., Denkewalter-type) possessing no interior void space. These two branch cell symmetry features were shown to be pivotal in directing internal packing modes; thereby, differentiating key dendrimer properties such as densities, refractive indices and interior porosities. Furthermore, this discovery provided an explanation for unimolecular micelle encapsulation (UME) behavior observed exclusively for Category I, but not for Category II. This account surveys early experiments confirming the inextricable influence of dendrimer branch cell symmetry on interior packing properties, first examples of Category (I) based UME behavior, nuclear magnetic resonance (NMR) protocols for systematic encapsulation characterization, application of these principles to the solubilization of active approved drugs, engineering dendrimer critical nanoscale design parameters (CNDPs) for optimized properties and concluding with high optimism for the anticipated role of dendrimer-based solubilization principles in emerging new life science, drug delivery and nanomedical applications.

Background: Limited data describe patient-reported outcomes (PROs) of localised oesophageal cancer treated with definitive chemoradiotherapy(CRT). The phase 2/3 SCOPE-1 trial assessed the effectiveness of CRT±cetuximab. The trial for the first time provided an opportunity to describe PROs from a multi-centre group of patients treated with CRT that are presented here., Methods: Patients undergoing CRT±cetuximab within the SCOPE-1 trial (258 patients from 36 UK centres) completed generic-, disease- and treatment-specific health-related quality of life (HRQL) questionnaires (EORTC QLQ-C30, QLQ-OES18, Dermatology Life-Quality Index (DLQI)) at baseline and at 7, 13, 24, 52 and 104 weeks. Mean EORTC functional scale scores (>15 point change significant), DLQI scores (>4 point change significant) and proportions of patients (>15% significant) with 'minimal' or 'severe' symptoms are presented., Results: Questionnaire response rates were good. At baseline, EORTC functional scores were high (>75%) and few symptoms were reported except for severe problems with fatigue, insomnia and eating-related symptoms (e.g., appetite loss, dysphagia, dry mouth) in both groups(>15%). Functional aspects of health deteriorated and symptoms increased with treatment and by week 13 global quality of life, physical, role and social function significantly deteriorated and more problems with fatigue, dyspnoea, appetite loss and trouble with taste were reported. Recovery occurred by 6 months (except severe fatigue and insomnia in >15% of patients) and maintained at follow-up with no differences between groups., Conclusions: CRT for localised oesophageal cancer has a significant detrimental impact on many aspects of HRQL; however, recovery is achieved by 6 months and maintained with the exception of persisting problems with severe fatigue and insomnia. The data suggest that the HRQL recovery after definitive CRT is quicker, and there is little lasting deficit compared with treatment including surgery. These data need to be compared with HRQL data from studies evaluating treatments including surgery for oesophageal cancer.

Background: Chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy.The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate), safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival., Methods/design: SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio.During Phase II of the study, the trial will assess safety (toxicity), activity (failure-free rate) and feasibility (recruitment rate and protocol dose modifications/delays) in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second stage will recruit a further 120 patients into each arm and compare the overall survival of both groups.All patients randomised into Phase II will contribute to the Phase III comparison of overall survival. In addition to overall survival, Phase III of the study will also assess toxicity, health related quality of life and cost effectiveness. A detailed radiotherapy protocol and quality assurance procedure has been incorporated into this trial., Trial Registration: ISRCTN: ISRCTN47718479.

Background: Pulmonary rehabilitation can improve the functional capacity, but has a variable effect on the low fat-free mass (FFM) in patients with chronic obstructive pulmonary disease., Hypothesis: Pulmonary rehabilitation would not affect catabolic drives such as systemic inflammation and also protein breakdown., Methods: Patients (n = 40) were studied at the start of an 8-week in-patient pulmonary rehabilitation programme, at the end of the programme and 4 weeks later. FFM and functional capacity (quadriceps strength, handgrip strength and peak workload) were assessed. Pseudouridine (PSU) urinary excretion (cellular protein breakdown) and inflammatory status were determined. Healthy participants had a single baseline assessment (n = 18)., Results: PSU, (IL)-6 and soluble tumour necrosis factor (sTNF)alpha R75 were increased in patients compared with healthy participants, whereas FFM and functional capacity were reduced (all p < 0.01). PSU was inversely related to both FFM and skeletal muscle function. FFM and functional parameters increased with rehabilitation, but PSU and inflammatory status were unaffected. The gain in FFM was lost 4 weeks after the completion of rehabilitation (p < 0.01)., Conclusion: The anabolic effect of pulmonary rehabilitation improved FFM, but it did not reverse the increased protein breakdown or systemic inflammation. Thus, on cessation of pulmonary rehabilitation the FFM gains were lost owing to a loss of anabolic drive.

Exercise is associated with release of inflammatory mediators in the circulation and there is evidence that the exercising muscles and tendons are sources of interleukin-6. Due to the catabolic effects of some cytokines, increased release in circulation might contribute to alterations in body composition in adults with cystic fibrosis. We hypothesised that exercise of moderate intensity would generate increased blood concentrations of some inflammatory mediators. We investigated the change in blood concentrations of interleukin-6, tumour necrosis factor alpha and their soluble receptors after a structured exercise (box stepping) of intensity similar to that encountered during activities of daily living in 12 adults with cystic fibrosis and mean (95% confidence interval) FEV1 55.6 (44.4, 66.8)% predicted, body mass index 23.0 (21.3, 24.6) kg/m2 and 12 healthy subjects. The increments post-exercise for all inflammatory mediators and lactate corrected for the work performed until voluntary exhaustion were greater for patients, while the total work was less for patients (all p<0.01). Daytime variability of the inflammatory mediators was assessed in eight patients and was less than the change due to exercise. We report greater increments in circulating concentrations of some cytokines with moderate exercise in adults with cystic fibrosis compared to healthy subjects.

Background: Weight loss indicates a poor prognosis in cystic fibrosis (CF). We hypothesised that fat-free mass (FFM) depletion and increased systemic inflammation would be associated with increased cellular proteolysis during an exacerbation of the respiratory symptoms. Patients were studied prospectively from the beginning of treatment with antibiotics when admitted to the Adults CF Centre., Methods: Twenty six patients with CF were studied at the start and end of antibiotic treatment and 2 weeks later. Mean (95% CI) FEV1 when clinically stable was 54.1 (44.5, 62.6)% predicted. Urinary excretion of Pseudouridine (5-ribosyluracil, PSU) was determined as an indicator of cellular protein breakdown. Body composition was assessed by dual energy X-ray absorptiometry (DXA)., Results: Patients had increased concentrations of PSU at all assessments (p<0.01). Those with a low FFM had greater PSU (ratio to FFMI) than those with a normal FFM at all assessments. At the start of treatment, PSU was related to FFM, C-reactive protein (CRP) (p<0.05) and tumour necrosis factor (TNF)alpha soluble receptors (sr) I and II (p<0.01). Circulating inflammatory mediators were greater in patients than in healthy subjects at all assessments., Conclusion: Increased protein breakdown is associated with a low FFM and increased systemic inflammation and it may be a contributory mechanism of poor weight preservation in CF.

The aim of this study was to determine whether repeated maximum inspiratory vital capacity manoeuvres against a fixed resistance increased effective short-term sputum clearance in adults with cystic fibrosis (CF). Twenty adults with CF were randomised to receive, on alternate days, either standardised physiotherapy (SP) for 30 min, comprising postural drainage and the active cycle of breathing technique, or a series of resistive inspiratory manoeuvres (RIM) at 80% of their maximum sustained inspiratory pressure developed between residual volume and total lung capacity during the first 4 days of the treatment of an exacerbation of respiratory symptoms. Expectorated sputum was collected during and for 30 min after each treatment and weighed. Total protein, immunoreactive interleukin (IL)-8 and human neutrophil elastase (HNE) concentrations, and the amount of each component expectorated, were determined. Compared with SP, RIM increased sputum weight two-fold, independent of treatment order or day. The concentrations of protein, IL-8 and HNE in sputum were similar for both treatments, while the quantity expectorated was greater with RIM treatment. In conclusion, short-term resistive inspiratory manoeuvres treatment was more effective at clearing sputum and inflammatory mediators than standardised physiotherapy.

Background: Weight loss is associated with reduced survival in patients with cystic fibrosis (CF)., Objective: We hypothesized that some adult patients with a normal body mass index (BMI) have evidence of hidden fat-free mass (FFM) and bone mineral density (BMD) depletion that is linked to more severe disease., Design: Fat mass (FM), FFM, and BMD were determined by dual-energy x-ray absorptiometry (DXA) and by bioelectric impedance in 56 adults in clinically stable condition and 20 age-matched healthy subjects. FM index and FFM index (FFMI) [kilograms per meter squared] of the right arm, leg, and trunk (ratio to height squared) were calculated. Lung function, including the maximum inspiratory pressure (MIP) and sustained MIP (SMIP), physical activity, serum C-reactive protein (CRP) and the number of exacerbations in the previous year were recorded., Results: Patients had a lower total FFM than healthy subjects (p < 0.01), while FM was similar. Of the 56 patients, 30 patients had a normal BMI, of which 12 patients had a low FFM (hidden loss) by DXA. The right arm, leg, and trunk FFMI and BMD at hip sites were less in these patients than in those with a normal BMI and normal FFM (all p < 0.01). This group had a lower FEV(1), SMIP, more frequent exacerbations, and greater circulating CRP (all p < 0.05)., Conclusions: In adults with CF, apparent or hidden loss of FFM, rather than weight loss, was related to overall disease severity. Hidden depletion of FFM was associated with increased loss of BMD and systemic inflammatory activity.

Increased survival in cystic fibrosis (CF) is associated with bone thinning and fat-free mass (FFM) loss. We hypothesized that the severity of lung disease would be associated with increased protein catabolism and systemic inflammatory status in clinically stable patients. Forty adults with CF and 22 age-matched healthy subjects were studied. Body composition was determined by dual-energy X-ray absorptiometry. Urinary pseudouridine (PSU), a marker of protein breakdown, and cross-linked N-telopeptides of type I collagen (NTx), a marker of bone connective tissue breakdown, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and their soluble receptors were measured. A 3-d food intake diary revealed 21 patients had a low energy intake. Excretion of PSU (p = 0.019) and NTx (p < 0.01) was increased in patients and was inversely related to FEV(1); PSU (r = - 0.53, p = 0.001) and NTx (r = - 0.43, p < 0.01). Increased excretion of PSU and NTx (p < 0.05 for both) was also related to a low FFM. All inflammatory mediators were greater in patients and were related to PSU and NTx. Clinically stable adults were catabolic with both cellular and connective tissue protein breakdown, which was related to lung disease severity, systemic inflammation, and body composition.

Weight loss in chronic obstructive airways disease (COPD) is associated with an increased energy cost of breathing. To determine an association between body composition and the inflammatory response we studied 80 clinically stable patients. Body composition was determined anthropometrically and skeletal muscle mass was determined as the creatinine-height index (CHI). Forty patients had their nitrogen balance determined. Circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and their soluble receptors were determined for 68 patients. Body mass index (BMI) was normal (> 20 kg/m(2)) in 55 patients, of whom 17 (31%) had a low CHI (< 80% predicted). A reduced CHI was associated with increased circulating levels of IL-6 (p = 0.001), TNF-alpha (p = 0.032) and their soluble receptors IL-6sr (p = 0.002), TNF-alpha sr1 (p = 0.03), and TNF-alpha sr2 (p = 0.001). Patients with a normal BMI and low CHI had inflammatory mediator levels similar to patients with a low BMI and CHI; both were significantly greater than in those with a normal BMI and CHI. Nitrogen balance was similar between normal and low CHI groups, although nitrogen excretion was significantly increased in the low CHI group. Skeletal muscle loss in COPD is probably multifactorial in origin, but our data suggest a link with systemic inflammation, even when weight loss is inapparent.

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores

Objectives: To determine the effect of an exacerbation of respiratory symptoms in cystic fibrosis (CF) on the activities of plasma benzoylcholinesterase and butyrylcholinesterase., Methods: Twenty-nine patients with CF in a respiratory exacerbation and 27 healthy volunteers matched for age and sex were recruited. Blood was obtained from the patients when commencing antibiotic treatment and 14 days later on completion of treatment. One blood sample was taken from the healthy volunteers. The activities of benzoylcholinesterase and butyrylcholinesterase were determined by spectrophotometric assay. The circulating inflammatory markers, C-reactive protein and neutrophil elastase-alpha1antiproteinase complex were also measured., Results: Benzoylcholinesterase activity was significantly (P = 0.001) lower in patients at the start of a respiratory exacerbation, compared with healthy controls [mean (SD): 917 (274) versus 1191(298) nmol x ml(-1) x min(-1)]. Benzoylcholinesterase activity increased significantly in patients to 1013 (237) nmol x ml(-1) x min(-1), following a course of antibiotic treatment (P = 0.006). Butyrylcholinesterase activity was also lower (P = 0.001) in patients at the start of a respiratory exacerbation, compared with healthy controls [5.54 (1.64) versus 7.01 (1.79) micromol x ml(-1) x min(-1)], and increased significantly in the patients to 6.31 (1.58) micromol x ml(-1) x min(-1) following treatment (P = 0.006)., Conclusion: We demonstrated significant suppression of plasma esterase activities during an exacerbation of respiratory symptoms in CF, which was only partially reversed after antibiotic treatment. Further studies are needed to examine other pathways of drug metabolism in this group of chronically infected patients.

Loss of body mass, which occurs in the later stages of cystic fibrosis (CF), probably affects all body compartments. We hypothesized that loss of skeletal muscle mass would include inspiratory muscles and impair their function. To test this, we determined the effect of body mass index (BMI) and lean body mass (LBM) depletion on handgrip (HG) force and inspiratory muscle function (IMF). The maximum inspiratory pressure (MIP) and the sustained maximum inspiratory pressure (SMIP) were measured with a computerized system. The relationship of IMF and reduced BMI to survival was studied in 49 patients, and a further 25 patients were studied to define the link between IMF and LBM. LBM was assessed by anthropometry. In the survival study a BMI < 20 kg/m2 was associated with a low SMIP (p < 0.001) and reduced survival, whereas MIP was relatively preserved. In the cross-sectional study SMIP (p < 0.001), MIP (p < 0.01), and HG (p < 0.01) were all reduced in the low LBM group, but not when related to total LBM. C-reactive protein and LBM were inversely related (r = -0.71, p < 0.01). Impaired IMF was chiefly a loss of sustained muscle contraction secondary to a reduced skeletal muscle mass, which may be related to pulmonary inflammation.

We measured circulating and sputum-sol concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase-alpha1-antiproteinase complex (NEAPC), and C-reactive protein (CRP) in an exacerbation, after antibiotic treatment, and in clinically stable patients with cystic fibrosis and chronic pulmonary infection with Pseudomonas aeruginosa. The aim was to determine the compartmental patterns of a proinflammatory and anti-inflammatory cytokine compared with other markers of inflammatory activity in cystic fibrosis. IL-6, NEAPC, CRP, and absolute neutrophil count were reduced after antibiotic treatment, p < 0.01. IL-6 and CRP concentrations were greater, p = 0.007, and p = 0.01, respectively, in a stable group of patients compared with those at the end of an exacerbation. IL-6 and CRP concentrations were related (r = 0.836, p < 0.0001), and both were greater than in matched control subjects (p < 0.001) at all times studied. Sputum-sol concentrations of IL-6 after treatment were positively related to FEV1 and FVC and inversely related to concentrations of neutrophil elastase. The separation between patients and healthy subjects, and the reduction of IL-6 after antibiotic treatment indicates it could be used as a marker of inflammation, but its relationship to other markers depends on the compartment in which it is measured.