No End in Sight? A Greenwash Review and Research Agenda.

Greenwashing is more virulent than ever. A profusion of environmental, social, and governance and net zero commitments are becoming fraught with questionable and misleading claims. At the same time, we are no closer to solving the pressing environmental and social issues of our time. In this review, we seek to examine this shift and summarize changes in greenwash research into three key phases: (a) 1.0 Static Communication; (b) 2.0 Dynamic Management; and (c) 3.0 Narratives about the Future. We analyze current key areas of developing literature and point to numerous open questions for future research. Next, we go beyond much of the published work to examine emerging tactics and lay out a forward-looking agenda for future research. We also propose a model of Corporate Miscommunication, integrating various streams in greenwash research. In doing so, we seek to lay a pathway for greenwashing researchers to finally find that elusive "end" to greenwashing.

Delphi consensus statement for understanding and managing the subcostal hernia: subcostal hernias collaborative report (scholar study).

INTRODUCTION: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias. METHODS: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement. RESULTS: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary. CONCLUSION: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias.

Single-dose pharmacokinetics and lung function of nebulized niclosamide ethanolamine in sheep.

PURPOSE: Niclosamide is approved as an oral anthelminthic, but its low oral bioavailability hinders its medical use requiring high drug exposure outside the gastrointestinal tract. An optimized solution of niclosamide for nebulization and intranasal administration using the ethanolamine salt has been developed and tested in a Phase 1 trial. In this study we investigate the pulmonary exposure of niclosamide following administration via intravenous injection, oral administration or nebulization. METHODS: We characterized the plasma and pulmonary pharmacokinetics of three ascending doses of nebulized niclosamide in sheep, compare it to intravenous niclosamide for compartmental PK modelling, and to the human equivalent approved 2 g oral dose to investigate in the pulmonary exposure of different niclosamide delivery routes. Following a single-dose administration to five sheep, niclosamide concentrations were determined in plasma and epithelial lining fluid (ELF). Non-compartmental and compartmental modeling was used to characterize pharmacokinetic profiles. Lung function tests were performed in all dose groups. RESULTS: Administration of all niclosamide doses were well tolerated with no adverse changes in lung function tests. Plasma pharmacokinetics of nebulized niclosamide behaved dose-linear and was described by a 3-compartmental model estimating an absolute bioavailability of 86%. ELF peak concentration and area under the curve was 578 times and 71 times higher with nebulization of niclosamide relative to administration of oral niclosamide. CONCLUSIONS: Single local pulmonary administration of niclosamide via nebulization was well tolerated in sheep and resulted in substantially higher peak ELF concentration compared to the human equivalent oral 2 g dose.

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial.

INTRODUCTION: Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects, including nausea, rash, photosensitivity, weight loss and fatigue. Reduced doses may be suboptimal in slowing disease progression. METHODS: This phase 1b, randomised, open-label, dose-response trial at 25 sites in six countries (Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618001838202) assessed safety, tolerability and efficacy of inhaled pirfenidone (AP01) in IPF. Patients diagnosed within 5 years, with forced vital capacity (FVC) 40%-90% predicted, and intolerant, unwilling or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulised AP01 50 mg once per day or 100 mg two times per day for up to 72 weeks. RESULTS: We present results for week 24, the primary endpoint and week 48 for comparability with published trials of antifibrotics. Week 72 data will be reported as a separate analysis pooled with the ongoing open-label extension study. Ninety-one patients (50 mg once per day: n=46, 100 mg two times per day: n=45) were enrolled from May 2019 to April 2020. The most common treatment-related adverse events (frequency, % of patients) were all mild or moderate and included cough (14, 15.4%), rash (11, 12.1%), nausea (8, 8.8%), throat irritation (5, 5.5%), fatigue (4, 4.4%) and taste disorder, dizziness and dyspnoea (three each, 3.3%). Changes in FVC % predicted over 24 and 48 weeks, respectively, were -2.5 (95% CI -5.3 to 0.4, -88 mL) and -4.9 (-7.5 to -2.3,-188 mL) in the 50 mg once per day and 0.6 (-2.2 to 3.4, 10 mL) and -0.4 (-3.2 to 2.3, -34 mL) in the 100 mg two times per day group. DISCUSSION: Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted. TRIAL REGISTRATION NUMBER: ACTRN12618001838202 Australian New Zealand Clinical Trials Registry.

Urostomal ileal conduit complications in association with abdominal wall mesh implantation.

OBJECTIVE: Parastomal hernia (PH) in association with an ileal conduit is a common complication that is difficult to treat. Mesh reinforcement has been suggested to improve outcomes; either as prophylaxis or for treatment of a parastomal hernia during abdominal wall reconstruction. PATIENTS AND METHODS: A retrospective study was performed in consecutive patients subjected to mesh implantation between 2000 and 2016 having a concurrent or previous ileal conduit reconstruction. Postoperative and late urostomal complications, as well as hernia occurrence, were ascertained by a chart review of patients' records. RESULTS: A total of 25 patients were included of whom 13 (52%) developed either a urostomal complication, a PH, or both. Complications were caused by mesh erosion in four patients, of which three were diagnosed more than five years after surgery. Four patients developed a urostomal stenosis. One out of eight patients with urostomal complications were subjected to a new ileal conduit reconstruction and another four to other types of revisional surgery. CONCLUSIONS: Every second patient with an ileal conduit developed either a local urostomal complication, a PH, or both after abdominal wall mesh reconstruction. A careful and cautious attitude towards the use of mesh in patients with an ileal conduit is suggested.

Waist Circumference is not Superior to Body Mass Index in Predicting Groin Hernia Repair in Either Men or Women.

BACKGROUND AND AIMS: A high body mass index (BMI) is considered a risk factor for ventral abdominal wall hernias but protective for the development of groin hernias. The reason for this is unclear. The surrounding abdominal fat in obesity might "protect" and limit the passage through the inguinal canal. The aim was to compare two different methods used for obesity registration in groin hernia patients and to investigate the hypothesis of high BMI/low groin hernia risk phenomenon. METHODS: This was a population-based observational study comparing BMI to waist circumference (WC) as well as their correlations to the quantity of groin hernia repair performed in either sex. Two national registers were crosslinked to a large regional register including information on WC. RESULTS: A larger WC and a higher BMI were associated with a lower risk of having groin hernia repair in both sexes. There was no difference using either WC or BMI as a risk factor for groin hernia repair in either sex. There was no advantage to using body composition based on WC rather than BMI for surgery indication. CONCLUSIONS: Overweight patients, both men and women, have a lower risk of undergoing groin hernia repair regardless of fat distribution. BMI is a well-established method for obesity registration and is recommended in the evaluation of hernia patients.

Guidelines for Treatment of Umbilical and Epigastric Hernias From the European and Americas Hernia Societies-A Web-Based Survey on Surgeons' Opinion.

Background and aims: The European and Americas Hernia Society's (EHS and AHS) Guidelines on the treatment of primary midline ventral hernias were launched to guide surgeons. As a part of a dissemination plan of the guideline, this study aimed to evaluate the level of consensus between recommendations and the current surgical practices of EHS and AHS members before implementation. Material and methods: A questionnaire was constructed including questions on the current practice of the members and nine selected key recommendations from the guidelines. An on-stage consensus voting was performed at the EHS Congress in Hamburg 2019 followed by a SurveyMonkey sent to all EHS and AHS members. Consensus with a recommendation was defined as an agreement of ≥70%. Results: A total of 178 votes were collected in Hamburg. A further 499/1,754 (28.4%) of EHS and 150/1,100 (13.6%) of AHS members participated in the SurveyMonkey. A consensus was reached for 7/9 (78%) of the recommendations. The two recommendations that did not reach consensus were on indication and the technique used for laparoscopic repair. In current practice, more AHS participants used a preformed patch; 50.7% (76/150) compared with EHS participants 32.1% (160/499), p < 0.001. Conclusion: A consensus was achieved for most recommendations given by the new guideline for the treatment of umbilical and epigastric hernias. Recommendations that did not reach consensus were on indication and technique for laparoscopic repair, which may reflect the lack of evidence on these topics.

European Hernia Society guidelines on management of rectus diastasis.

BACKGROUND: The definition, classification and management of rectus diastasis (RD) are controversial in the literature and a variety of different surgical treatments have been described. This article reports on the European Hernia Society (EHS) Clinical Practice Guideline for RD. METHOD: The Guideline group consisted of eight surgeons. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done in November 2018 and updated in November 2019 and October 2020. Nine Key Questions (KQs) were formulated. RESULTS: Literature reporting on the definition, classification, symptoms, outcomes and treatments was limited in quality, leading to weak recommendations for the majority of the KQs. The main recommendation is to define RD as a separation between rectus muscles wider than 2 cm. A new classification system is suggested based on the width of muscle separation, postpregnancy status and whether or not there is a concomitant hernia. Impaired body image and core instability appear to be the most relevant symptoms. Physiotherapy may be considered before surgical management. It is suggested to use linea alba plication in patients without concomitant hernia and a mesh-based repair of RD with concomitant midline hernias. CONCLUSION: RD should be defined as a separation of rectus muscles wider than 2 cm and a new classification system is suggested.

The management of RD is controversial. These guidelines are intended to provide a consensus about the exact definition, the correct way of measurement and diagnosis, a classification system, the main symptoms, and a systematic review of non-surgical and surgical treatments to achieve the best results for patients with this pathology. The main recommendation is to define RD as a separation between rectus muscles wider than 2 cm. A new classification system is proposed. It is suggested to use linea alba plication in patients without concomitant hernia and a mesh-based repair of RD in those with concomitant midline hernias.

Perioperative optimization in complex abdominal wall hernias: Delphi consensus statement.

BACKGROUND: The incidence of incisional hernia after major abdominal surgery via a midline laparotomy is 20-41 per cent with short-term follow-up, and over 50 per cent in those surviving an abdominal catastrophe. Abdominal wall reconstruction (AWR) requires complex operations, often involving mesh resection, management of scarred skin, fistula takedown, component separation or flap reconstruction. Patients tend to have more complex conditions, with multiple co-morbidities predisposing them to a vicious cycle of complications and, subsequently, hernia recurrence. Currently there appears to be variance in perioperative practice and minimal guidance globally. The aim of this Delphi consensus was to provide a clear benchmark of care for the preoperative assessment and perioperative optimization of patients undergoing AWR. METHODS: The Delphi method was used to achieve consensus from invited experts in the field of AWR. Thirty-two hernia surgeons from recognized hernia societies globally took part. The process included two rounds of anonymous web-based voting with response analysis and formal feedback, concluding with a live round of voting followed by discussion at an international conference. Consensus for a strong recommendation was achieved with 80 per cent agreement, and a weak recommendation with 75 per cent agreement. RESULTS: Consensus was obtained on 52 statements including surgical assessment, preoperative assessment, perioperative optimization, multidisciplinary team and decision-making, and quality-of-life assessment. Forty-six achieved over 80 per cent agreement; 14 statements achieved over 95 per cent agreement. CONCLUSION: Clear consensus recommendations from a global group of experts in the AWR field are presented in this study. These should be used as a baseline for surgeons and centres managing abdominal wall hernias and performing complex AWR.

Reporting guideline for interventional trials of primary and incisional ventral hernia repair.

BACKGROUND: Primary and incisional ventral hernia trials collect unstandardized inconsistent data, limiting data interpretation and comparison. This study aimed to create two minimum data sets for primary and incisional ventral hernia interventional trials to standardize data collection and improve trial comparison. To support these data sets, standardized patient-reported outcome measures and trial methodology criteria were created. METHODS: To construct these data sets, nominal group technique methodology was employed, involving 15 internationally recognized abdominal wall surgeons and two patient representatives. Initially a maximum data set was created from previous systematic and panellist reviews. Thereafter, three stages of voting took place: stage 1, selection of the number of variables for data set inclusion; stage 2, selection of variables to be included; and stage 3, selection of variable definitions and detection methods. A steering committee interpreted and analysed the data. RESULTS: The maximum data set contained 245 variables. The three stages of voting commenced in October 2019 and had been completed by July 2020. The final primary ventral hernia data set included 32 variables, the incisional ventral hernia data set included 40 variables, the patient-reported outcome measures tool contained 25 questions, and 40 methodological criteria were chosen. The best known variable definitions were selected for accurate variable description. CT was selected as the optimal preoperative descriptor of hernia morphology. Standardized follow-up at 30 days, 1 year, and 5 years was selected. CONCLUSION: These minimum data sets, patient-reported outcome measures, and methodological criteria have allowed creation of a manual for investigators aiming to undertake primary ventral hernia or incisional ventral hernia interventional trials. Adopting these data sets will improve trial methods and comparisons.

Presumptive neural microsporidiosis in a young adult German Shepherd dog from rural Australia.

CASE REPORT: A 1-year-old, neutered male German Shepherd was presented with a 5-month history of episodic lethargy, intermittent fever, weight loss and a hunched posture. The dog was diagnosed with presumptive microsporidian meningoencephalitis based on cytological findings on cerebrospinal fluid analysis and a positive PCR test. The dog initially responded favourably to a 4-week course of trimethoprim-sulfadiazine, pyrimethamine and fenbendazole, and remained well for 12 weeks following cessation of treatment. Disease then recurred, and despite an initial positive response to treatment, he deteriorated and was euthanased 11 weeks later, 7.5 months after definitive diagnosis and 13 months after clinical signs were first reported. CONCLUSION: To the authors knowledge, this is the first case of canine microsporidiosis in Australia.

A systematic review of outcome reporting in incisional hernia surgery.

BACKGROUND: The incidence of incisional hernia is up to 20 per cent after abdominal surgery. The management of patients with incisional hernia can be complex with an array of techniques and meshes available. Ensuring consistency in reporting outcomes across studies on incisional hernia is important and will enable appropriate interpretation, comparison and data synthesis across a range of clinical and operative treatment strategies. METHODS: Literature searches were performed in MEDLINE and EMBASE (from 1 January 2010 to 31 December 2019) and the Cochrane Central Register of Controlled Trials. All studies documenting clinical and patient-reported outcomes for incisional hernia were included. RESULTS: In total, 1340 studies were screened, of which 92 were included, reporting outcomes on 12 292 patients undergoing incisional hernia repair. Eight broad-based outcome domains were identified, including patient and clinical demographics, hernia-related symptoms, hernia morphology, recurrent incisional hernia, operative variables, postoperative variables, follow-up and patient-reported outcomes. Clinical outcomes such as hernia recurrence rates were reported in 80 studies (87 per cent). A total of nine different definitions for detecting hernia recurrence were identified. Patient-reported outcomes were reported in 31 studies (34 per cent), with 18 different assessment measures used. CONCLUSIONS: This review demonstrates the significant heterogeneity in outcome reporting in incisional hernia studies, with significant variation in outcome assessment and definitions. This is coupled with significant under-reporting of patient-reported outcomes.

Spontaneous hemopneumothorax in an adolescent with COVID-19.

As coronavirus disease 2019 (Covid-19) continues to spread world-wide, new symptoms associated with the disease continue to appear. Common manifestations include fever, shortness of breath, and gastrointestinal illness. In addition, COVID is known to induce coagulopathy. Here, we present the case of a 17-year-old male who presented with a massive hemopneumothorax and was found to incidentally be positive for Covid-19. We suspect that he had a primary pneumothorax from a bleb and the hemothorax could've been induced by the coagulopathic state induced by COVID infection.

Routine versus selective intraoperative cholangiography during cholecystectomy: systematic review, meta-analysis and health economic model analysis of iatrogenic bile duct injury.

BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy. Early recognition and treatment of BDI has been shown to reduce costs and improve patients' quality of life. The aim of this study was to assess the effect and cost-effectiveness of routine versus selective intraoperative cholangiography (IOC) in cholecystectomy. METHODS: A systematic review and meta-analysis, combined with a health economic model analysis in the Swedish setting, was performed. Costs per quality-adjusted life-year (QALY) for routine versus selective IOC during cholecystectomy for different scenarios were calculated. RESULTS: In this meta-analysis, eight studies with more than 2 million patients subjected to cholecystectomy and 9000 BDIs were included. The rate of BDI was estimated to 0.36 per cent when IOC was performed routinely, compared with to 0.53 per cent when used selectively, indicating an increased risk for BDI of 43 per cent when IOC was used selectively (odds ratio 1.43, 95 per cent c.i. 1.22 to 1.67). The model analysis estimated that seven injuries were avoided annually by routine IOC in Sweden, a population of 10 million. Over a 10-year period, 33 QALYs would be gained at an approximate net cost of €808 000 , at a cost per QALY of about €24 900. CONCLUSION: Routine IOC during cholecystectomy reduces the risk of BDI compared with the selective strategy and is a potentially cost-effective intervention.

An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Inhalation: A means to explore and optimize nintedanib's pharmacokinetic/pharmacodynamic relationship.

Oral nintedanib is marketed for the treatment of idiopathic pulmonary fibrosis (IPF). While effective slowing fibrosis progression, as an oral medicine nintedanib is limited. To reduce side effects and maximize efficacy, nintedanib was reformulated as a solution for nebulization and inhaled administration. To predict effectiveness treating IPF, the nintedanib pharmacokinetic/pharmacodynamic relationship was dissected. Pharmacokinetic analysis indicated oral-delivered nintedanib plasma exposure and lung tissue partitioning were not dose-proportional and resulting lung levels were substantially higher than blood. Although initial-oral absorbed nintedanib efficiently partitioned into the lung, only a quickly eliminated fraction appeared available to epithelial lining fluid (ELF). Because IPF disease appears to initiate and progress near the epithelial surface, this observation suggests short duration nintedanib exposure (oral portion efficiently partitioned to ELF) is sufficient for IPF efficacy. To test this hypothesis, exposure duration required for nintedanib activity was explored. In vitro, IPF-cellular matrix (IPF-CM) increased primary normal human fibroblast (nHLF) aggregate size and reduced nHLF cell count. IPF-CM also increased nHLF ACTA2 and COL1A expression. Whether short duration (inhalation pharmacokinetic mimic) or continuous exposure (oral pharmacokinetic mimic), nintedanib (1-100 nM) reversed these effects. In vivo, intubated silica produced a strong pulmonary fibrotic response. Once-daily (QD) 0.021, 0.21 and 2.1 mg/kg intranasal (IN; short duration inhaled exposure) and twice-daily (BID) 30 mg/kg oral (PO; long duration oral exposure) showed that at equivalent-delivered lung exposure, QD short duration inhaled nintedanib (0.21 mg/kg IN vs. 30 mg/kg PO) exhibited equivalent-to-superior activity as BID oral (reduced silica-induced elastance, alpha-smooth muscle actin, interleukin-1 beta (IL-1ß) and soluble collagen). Comparatively, the increased inhaled lung dose (2.1 mg/kg IN vs. 30 mg/kg PO) exhibited increased effect by further reducing silica-induced elastance, IL-1ß and soluble collagen. Neither oral nor inhaled nintedanib reduced silica-induced parenchymal collagen. Both QD inhaled and BID oral nintedanib reduced silica-induced bronchoalveolar lavage fluid macrophage and neutrophil counts with oral achieving significance. In summary, pharmacokinetic elements important for nintedanib activity can be delivered using infrequent, small inhaled doses to achieve oral equivalent-to-superior pulmonary activity.