Moving towards fully circular insect production: A focus on insect-derived biowastes.

Over the last decade, commercialization of insects for food and feed has been exponentially increasing. Insect protein is emerging as a sustainable livestock feed and human food alternative due to its low land and carbon footprint. The principles of insect industry are deeply embedded in the core values of sustainability and circular economy. Black soldier fly (BSF) is the crown jewel of insect industry and is one of the most commercially farmed insects. However, this steadfast growth is accompanied by generation of insect based biowaste such as dead flies and pupae exuviae. This will be a major waste fraction from this industry. This study discusses the valorization potential of this waste into chitin (which finds application in cosmetics, bioplastics, and pesticides, among other industries), biogas, fertilizer, and biochar. There is need to conduct more explorative research on value proposition of insect based biowaste to ensure that this industry can comply fully with circular economy and sustainability principles.

Associations between the EQ-5D-5L and exacerbations of chronic obstructive pulmonary disease in the ETHOS trial.

PURPOSE: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with deteriorating health and health-related quality of life (HRQoL) among people with COPD during and after events. HRQoL data are key to evaluating treatment cost-effectiveness and informing reimbursement decisions in COPD. EuroQoL 5-dimension 5-level (EQ-5D-5L) utility scores, based on various HRQoL measures, are used in economic evaluations of pharmacotherapy. These analyses estimated associations between EQ-5D-5L utility scores and exacerbations (new and previous) in patients with moderate-to-very severe COPD. METHODS: Longitudinal mixed models for repeated measures (MMRM), adjusted for time and treatment, were conducted using data from the ETHOS study (NCT02465567); models regressed EQ-5D-5L on current and past exacerbations that occurred during the study, adjusting for other patient reported outcomes and clinical factors. RESULTS: Based on the simplest covariate adjusted model (adjusted for current exacerbations and number of previous exacerbations during the study), a current moderate exacerbation was associated with an EQ-5D-5L disutility of 0.055 (95% confidence interval: 0.048, 0.062) with an additional disutility of 0.035 (0.014, 0.055) if the exacerbation was severe. After resolving, each prior exacerbation was associated with a disutility that persisted for the remainder of the study (moderate exacerbation, 0.014 [0.011, 0.016]; further disutility for severe exacerbation, 0.011 [0.003, 0.018]). CONCLUSION: An EQ-5D-5L disutility of 0.090 was associated with a current severe exacerbation in ETHOS. Our findings suggest incorporating the effects of current, recently resolved, and cumulative exacerbations into economic models when estimating benefits and costs of COPD pharmacotherapy, as exacerbations have both acute and persistent effects.

Performance evaluation of black soldier fly larvae fed on human faeces, food waste and their mixture.

In this study, Black Soldier Fly Larvae (BSFL)-based technology has been proposed and tested for treatment and valorization of human faeces, food waste and a mixture of 75% human faeces with 25% food waste. Experiments were conducted between 15 and 45 °C and 55-75% relative humidity. BSFL's performance for the degradation of the mixed waste was significantly better than their performances when used for the degradation of either human faeces or food waste fed alone, primarily due to the availability of more conducive pH, and better microbial and nutrient balance. The abiotic factors, temperature and relative humidity impacted the decomposition rate and weight gain pattern of BSFL when they were fed on the waste streams. The results showed that the optimum conditions to conduct the proposed BSFL-based treatment was 31-35 °C and 55-75% RH. The protein content in the BSFL was not impacted significantly by the quality of the waste stream, whereas the fat content varied substantially. The abiotic factors also impacted the protein and fat content of BSFL. The investigation led to the estimation of the decomposition rates over a wide range of temperature and relative humidity conditions, which could be useful for the design of large-scale BSFL-based treatment plants.

Black soldier fly larvae for treatment and segregation of commingled municipal solid waste at different environmental conditions.

The commingled nature of the municipal solid waste in many developing nations is one of the primary reasons behind the failure to its successful management. Although there are technologies to effectively treat and process well-segregated and classified waste, they are ineffective in managing the commingled waste. Commingled waste has neither calorific value enough to support waste-to-energy operations nor is it suitable for producing quality compost to generate market value. In this article, a novel Black Soldier Fly Larva (BSFL) -based technology has been proposed and tested to auto-segregate and treat the biodegradable fraction of the Commingled Municipal Solid Waste (CMSW). Several BSFL feeding experiments on five different CMSW compositions were conducted at various temperatures and relative humidity conditions. BSFL could selectively consume the biodegradable fraction of the CMSW to convert it into its body mass and separate itself from the rest of the waste, which mainly consisted of inert and recyclable waste fractions that can be further treated using appropriate waste treatment technology. The mature larvae or the pre-pupae grown at the expense of the biodegradable waste fraction can find several commercial uses. The larvae's consumption rate and weight gain were dependent on the environmental conditions; 30 °C and relative humidity of 65-75% provided the highest consumption rate and most significant weight gain. The batch experiments in the laboratory proved that BSFL could be promising for the treatment of CMSW. The experimental data presented may help design a process for further scaling up an effective treatment method for CMSW, which might benefit many developing nations in managing their waste effectively and economically.

Cost-effectiveness of roflumilast as an add-on to triple inhaled therapy vs triple inhaled therapy in patients with severe and very severe COPD associated with chronic bronchitis in the UK.

Purpose: Patients with severe COPD are at high risk of experiencing disease exacerbations, which require additional treatment and are associated with elevated mortality and increased risk of future exacerbations. Some patients continue to experience exacerbations despite receiving triple inhaled therapy (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled therapy for these patients. This cost-effectiveness analysis compared costs and quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple inhaled therapy alone, using data from the REACT and RE2SPOND trials. Patients and methods: Patients included in the analysis had severe to very severe COPD, FEV1 <50% predicted, symptoms of chronic bronchitis and ≥2 exacerbations per year. Our model was adapted from a previously published and validated model, and the analyses conducted from a UK National Health Service perspective. A scenario analysis considered a subset of patients who had experienced at least one COPD-related hospitalization within the previous year. Results: Roflumilast as add-on to triple inhaled therapy was associated with non-significant reductions in rates of both moderate and severe exacerbations compared with triple inhaled therapy alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on to triple inhaled therapy was £24,976. In patients who had experienced previous hospitalization, roflumilast was associated with a non-significant reduction in the rate of moderate exacerbations, and a statistically significant reduction in the rate of severe exacerbations. The ICER for roflumilast in this population was £7,087. Conclusions: Roflumilast is a cost-effective treatment option for patients with severe or very severe COPD, chronic bronchitis, and a history of exacerbations. The availability of roflumilast as add-on treatment addresses an important unmet need in this patient population.

Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease (ROBERT): a 16-week, randomised, placebo-controlled trial.

BACKGROUND: The clinical effects of roflumilast, a selective phosphodiesterase-4 inhibitor, are well established, but little is known about the anti-inflammatory mechanisms underlying the drug's efficacy. The aim of the ROflumilast Biopsy European Research Trial (ROBERT) was to assess the anti-inflammatory effects of roflumilast on bronchial mucosal inflammation in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and chronic bronchitis. METHODS: ROBERT was a randomised, double-blind, placebo-controlled trial done at 18 sites in five countries. Eligible patients were aged 40-80 years, had COPD, and had had a chronic productive cough for 3 months in each of the two previous years. Patients also had to have a post-bronchodilator predicted FEV1 30-80% and a post-bronchodilator FEV1/forced vital capacity ratio of 70% or less. Patients entered a 6-week run-in period before being randomly assigned (1:1) via a computerised central randomisation system to roflumilast 500 µg once daily or placebo for 16 weeks, in addition to bronchodilator therapy (inhaled corticosteroids were not permitted). Randomisation was stratified by concomitant use of long-acting ß agonist. Both participants and investigators were masked to group assignment. Roflumilast and placebo were supplied as identical yellow, triangular tablets. Airway inflammation was assessed by quantification of inflammatory cells in bronchial biopsy samples and induced sputum samples. The primary endpoint was the change in the number of CD8 inflammatory cells in bronchial biopsy submucosa from randomisation to week 16 in the intention-to-treat population. Changes in cell counts of additional inflammatory markers, including eosinophils, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov, number NCT01509677, and is closed to new participants, with follow-up completed. FINDINGS: Between Jan 4, 2012, and Feb 11, 2016, 158 patients were randomly assigned: 79 to the roflumilast group, and 79 to the placebo group. At week 16, the change in the number of CD8 cells in the bronchial submucosa did not differ significantly between the roflumilast and placebo groups (treatment ratio 1·03 [95% CI 0·82-1·30]; p=0·79). However, compared with placebo, roflumilast was associated with a significant reduction in eosinophils in bronchial biopsy samples at week 16 (treatment ratio 0·53 [95% CI 0·34-0·82]; p=0·0046). Significant reductions in both absolute (p=0·0042) and differential (p=0·0086) eosinophil cell counts in induced sputum were also noted with roflumilast compared with placebo, but peripheral blood eosinophil counts were not significantly affected. We noted no other significant effects of roflumilast on bronchial mucosal inflammatory cells. The most common (ie, occurring in >5% patients) moderate adverse events were worsening of COPD (three [4%] patients in the roflumilast group vs seven [9%] in the placebo group), cough (six [8%] vs four [5%]), diarrhoea (four [5%] vs three [4%]), and nasopharyngitis (three [4%] vs five [6%]). Severe adverse events included worsening of COPD, which occurred in four (5%) patients in the roflumilast group and two (3%) in the placebo group. No deaths occurred during the study. Serious adverse events occurred in eight (10%) patients in the roflumilast group and five (6%) in the placebo group. INTERPRETATION: 16 weeks of treatment with roflumilast did not affect the number of CD8 cells in bronchial submucosa compared with placebo. However, we noted significant reductions in eosinophil cell counts in bronchial biopsy samples and induced sputum, generating the hypothesis that the effect of roflumilast in COPD could be mediated by an effect on lung eosinophils. FUNDING: Takeda and AstraZeneca.

Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease. Pooled Analysis of Two Randomized Trials.

RATIONALE: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted. OBJECTIVES: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast. METHODS: Predefined, pooled analyses of REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment; NCT01329029) and RE2SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy; NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year. MEASUREMENTS AND MAIN RESULTS: In the overall intention-to-treat population (n = 4,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80-0.97; P = 0.0086) and severe exacerbations by 16.1% (0.84; 0.71-0.99; P = 0.0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63-0.88; P = 0.0005); had more than two exacerbations in the prior year (0.79; 0.65-0.96; P = 0.0160); or had baseline eosinophils ≥150 cells/µl (0.81; 0.71-0.93; P = 0.0020), ≥150 to <300 cells/µl (0.84; 0.71-0.98; P = 0.0282), or ≥300 cells/µl (0.77; 0.61-0.97; P = 0.0264). Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at ≥150 cells/µl (0.65; 0.52-0.82; P = 0.0003) and 42.7% at ≥300 cells/µl (0.57; 0.37-0.88; P = 0.0111) versus placebo. CONCLUSIONS: This prespecified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher (≥150 cells/µl, ≥150 to <300 cells/µl, or ≥300 cells/µl) baseline blood eosinophil count.