Practical Things You Should Know about Wound Healing and Vacuum-Assisted Closure Management.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Understand the basics of negative-pressure wound therapy and practical uses of various vacuum-assisted closure dressings. 2. Understand the mechanisms of action of negative-pressure therapies and other important adjuncts, such as perfusion imaging. 3. Discuss the evidence for hyperbaric oxygen therapy in wound care. SUMMARY: Wound healing requires creating an environment that supports the healing process while decreasing inflammation and infection. Negative-pressure wound therapy has changed the way physicians manage acute and chronic wounds for more than 20 years. It contracts wound edges, removes exudate, including inflammatory and infectious material, and promotes angiogenesis and granulation tissue formation. These effects have been consistently demonstrated in multiple animal and human randomized controlled trials. Recent innovations that include instillation therapy and closed incision have further increased our arsenal against difficult-to-treat wounds and incisions at high risk of complications. Instillation of topical wound solutions allows physicians to cleanse the wound without return to the operating room, resulting in fewer debridements, shorter hospital stays, and faster time to wound closure. Other concepts have yielded negative-pressure therapy on top of closed surgical incisions, which holds incision edges together, reduces edema, promotes angiogenesis, and creates a barrier to protect incisions during the critical healing period, thereby reducing surgical-site complications, especially infection. Other practical adjuncts to the modern-day treatment of acute and chronic wounds include indocyanine green angiography, which allows real-time assessment of perfusion, and hyperbaric oxygen treatment, which has been suggested to augment healing in acute, chronic, specifically diabetic foot ulcers and radiation-related wounds.

Oral Contraceptive Management in Aesthetic Surgery: A Survey of Current Practice Trends.

BACKGROUND: Oral contraceptive pills (OCPs) are currently used by approximately 16% of all women aged 15 to 44 in the United States and have been used by 80% of all sexually active women at some point in their lives. However, no guidelines exist for discontinuation of OCP therapy before or after elective cosmetic surgery. OBJECTIVES: The aim of this study is to establish current practice trends regarding perioperative OCP management in aesthetic surgery. METHODS: An eight-item online survey was distributed to members of the American Society of Plastic Surgeons (ASPS). Survey results were analyzed to determine if surgeons' practice setting, years of experience, annual cosmetic volume, or types of cosmetic procedures performed affected their perioperative management of OCPs. RESULTS: A total of 220 questionnaires were collected (11.9% response rate). Only 31.8% of surgeons reported any discontinuation of OCPs pre- or postoperatively. Among physicians, 7.3% reported only preoperative discontinuation, 24.5% reported OCP discontinuation both pre- and postoperatively, and 0.0% of physicians reported discontinuation of OCPs only postoperatively. There was no statistically significant difference between the percentage of surgeons in academic practice who discontinue OCPs perioperatively (P = 0.335). There was no statistical significance towards overall years in practice (P = 0.152). There were no significant differences between the three groups in the number of cosmetic procedures performed annually or percentage breakdown of procedures performed. CONCLUSIONS: Despite OCP therapy being a known risk factor for venous thromboembolic events, a majority of surgeons performing cosmetic surgery do not routinely recommend perioperative cessation.

Antimicrobial Prophylaxis Practice Patterns in Breast Augmentation: A National Survey of Current Practice.

BACKGROUND: Breast augmentation is one of the most commonly performed aesthetic surgery procedures worldwide. Bacterial contamination is of paramount concern due to its role in biofilm formation and capsular contracture. Plastic surgeons have adopted a variety of perioperative interventions in efforts to reduce implant contamination, however definitive evidence supporting these practices is lacking. OBJECTIVE: The goal of this study was to assess current practice patterns aimed at reducing implant-related infections in breast augmentation and comparing them to current evidence-based medicine recommendations. METHODS: A 20-question survey assessing practices aimed at preventing breast implant associated infections was generated and distributed via SurveyMonkey to members of the American Society of Plastic Surgery whose electronic mail addresses were listed on the American Society of Plastic Surgery member website in April 2015. RESULTS: A total of 253 responses were received from the survey. Of the respondents, 81% were in private practice. Respondents averaged 21 ± 9 years in practice, and 69 ± 111 breast augmentations performed per year. A majority of surgeons used Chlorhexidine to prepare the surgical site (45%) and triple antibiotic solution both as a soak for the implant before placement (40%) as well as for implant pocket irrigation (47%). A no-touch technique using the Keller Funnel was adopted by 42% of surgeons. Regarding antibiotic use in the postoperative period, first-generation cephalosporins were used by the majority of respondents (79%), and the most common duration was for 4 to 6 days (45%). CONCLUSIONS: Although there is heterogeneity in specific aspects of antimicrobial prophylaxis during breast augmentation, there is a clear trend toward practice modification geared towards preventing bacterial contamination in breast augmentation. Surgeons may benefit from high-level studies designed to create standardized evidence-based practice guidelines.

Preventing Breast Implant Contamination in Breast Reconstruction: A National Survey of Current Practice.

BACKGROUND: Implant-based breast reconstruction is commonly performed by plastic surgeons worldwide. Bacterial contamination is of paramount concern because of its role in biofilm formation and capsular contracture. Plastic surgeons have adopted a variety of perioperative interventions in efforts to reduce implant contamination; however, definitive evidence supporting these practices is lacking. OBJECTIVE: The goal of this study was to assess current practice patterns aimed at reducing implant-related infections. METHODS: A 20-question survey assessing practices aimed at preventing breast implant-associated infections was generated and distributed via SurveyMonkey to members of the American Society of Plastic Surgery whose e-mail addresses were listed on the American Society of Plastic Surgery member Web site in April 2015. RESULTS: A total of 1979 invitations to participate in the survey were sent, and 253 responses were received during the 4-month study period. Of respondents, 81% were in private practice. Respondents averaged 21 ± 9 years in practice, and 34 ± 50 implant-based breast reconstructions were performed per year. A majority of surgeons used chlorhexidine to prepare the surgical site (52%), a triple antibiotic soak for the implant prior to placement (50%) and povidone-iodine for implant pocket irrigation (44%). A no-touch technique utilizing the Keller funnel was adopted by 69% of surgeons. Regarding antibiotic use in the postoperative period, first-generation cephalosporins (eg, cephalexin, cefadroxil) were used by a majority of surgeons (84%), and the most common duration was until drain removal (45%). CONCLUSIONS: There is considerable heterogeneity in surgical practices aimed at preventing bacterial contamination in implant-based breast reconstruction. Surgeons may benefit from high-level studies designed to create standardized evidence-based practice guidelines.

Comparison of free fibular flaps with reamer-irrigator-aspirator bone grafts for the reconstruction of critical-sized mandibular defects.

OBJECTIVE: Vascularized bone flaps are currently indicated for reconstructing mandibular defects 6 cm or larger. This technique can result in donor-site morbidity and requires microsurgery. To explore alternative methods of mandibular reconstruction, we sought to compare bone graft obtained with the reamer-irrigator-aspirator (RIA) device with the free fibula (FF) flap for the reconstruction of a critical-sized mandibular defect. METHODS: Sixteen 3-month-old Yorkshire pigs underwent 6-cm full-thickness resection of the left mandible. For the FF group (n = 8), an osseous FF flap was raised from the left leg and placed into the defect. For the RIA group (n = 8), a RIA Instrument Set was used on the ipsilateral femur to ream the femoral canal and harvest RIA putty. This putty containing medullary bone marrow contents and cortical bone was packed into the defect. At the study end point, volumetric, biomechanical, and histologic analyses were performed. RESULTS: Operative times were significantly shorter in the RIA group (RIA,126 [30] min; FF, 346 [50] min; P < 0.05). Biomechanical testing of reconstructed sites showed no significant difference in maximum fracture loads between both groups (RIA, 468 [97] N; FF, 689 [262] N; P = 0.11). Mean (SD) volume ratio of bone growth at the reconstructed sites was comparable between both groups (RIA, 71% [4.5%]; FF, 72% [3.3%]; P = 0.60). Equal bone quality was confirmed histologically. CONCLUSIONS: The RIA technique significantly reduces operative time and provides bone of equal strength and histologic quality to FF flap reconstruction in a large animal model. The RIA method may represent an efficient technique for the reconstruction of craniomaxillofacial defects.

Reconstruction of porcine critical-sized mandibular defects with free fibular flaps: the development of a craniomaxillofacial surgery model.

Vascularized bone flaps are the well-known standards of care for reconstruction of segmental mandibular defects ≥ 6 cm. We developed a large animal critical-sized mandibular defect model in which osseous free fibula flaps were used for reconstruction.In this study a total of eight 3-month-old Yorkshire pigs underwent 6 cm full-thickness resection of the left hemimandible. An osseous free fibula flap from the left leg was harvested and contoured to the mandibular defect. Bone placement and plate position was confirmed with fluoroscopy. Animals were followed with serial radiographs and clinical evaluations.Free fibulas were transferred successfully in all eight animals. The average operative time was 346 minutes, and the average flap ischemia time was 86 minutes. The average volume ratio of reconstructed hemimandibles to nonoperated control hemimandibles was 0.72 ± 0.33. The average maximum fracture load was 689 ± 262 N, and the average ratio of biomechanical fracture load for these samples compared with contralateral control hemimandibles was 0.88 ± 0.25.It is concluded that the porcine osseous free fibula flaps can be reliably harvested and viably transferred to critical-sized posterior mandibular defects with acceptable long-term results. The described microsurgical large animal model is acceptable for use in craniomaxillofacial experimentation.

Found in space: computer-assisted orthognathic alignment of a total face allograft in six degrees of freedom.

PURPOSE: Full facial osteomyocutaneous transplantation requires correct 3-dimensional (3D) alignment of donor osseous structures to a new cranial base with minimal reference points and 6 degrees of potential movement. We investigated whether computer-assisted design and manufacturing (CAD/CAM) could enable accurate placement of the facial skeleton. MATERIALS AND METHODS: A prospective single-cohort study of Le Fort III-based maxillary-mandibular segment allotransplantation was performed in 5 cadaver pairs and 1 clinical pair. The osteotomies were modeled using computed tomography (CT) data and 3D modeling software and then translated to the donor-recipient pairs using surgical navigation and osteotomy cutting guides. The predicted values were calculated about all rotational axes (pitch, yaw, and roll) and along all translational axes (vertical, horizontal, and anteroposterior) and used as the independent variable. The primary outcome variable of the actual postoperative CT values was compared for fidelity to the prediction using the intraclass correlation coefficient (ICC). The similarity to the donor versus recipient values was calculated as a secondary independent variable, and both predicted and actual measurements were compared with it as a percentage. RESULTS: The postoperative fidelity to the plan was adequate to excellent (ICC 0.520 to 0.975) with the exception of lateral translation (2.94 ± 1.31 mm predicted left vs 3.92 ± 2.17 mm right actual displacement; ICC 0.243). The predicted and actual values were not consistently skewed toward the donor or recipient values. CONCLUSIONS: We have demonstrated a novel application of CAD/CAM that enables orthognathic alignment of a maxillary-mandibular segment to a new cranial base. Quantification of the alignment in all 6 degrees of freedom delivers precise control compared with the planned changes and allows postoperative quality control.

Long-term vascular, motor, and sensory donor site outcomes after ulnar forearm flap harvest.

Use of the ulnar forearm flap (UFF) is limited by concerns for ulnar nerve injury and impaired perfusion in the donor extremity. Twenty UFFs were performed over a 6-year period. All patients underwent postoperative bilateral upper extremity arterial duplex studies. A subset of postoperative patients (n = 10) also had bilateral upper extremity sensory and motor evaluations, and functional evaluation via the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH). Motor function was tested by digital and key grip dynamometry. Ulnar nerve sensation was tested by evaluation of one- and two-point perceived pressure thresholds and two-point discrimination using the Pressure-Specified Sensory Device (Sensory Management Services, LLC, Baltimore, MD). All UFFs were viable postoperatively. Mean follow-up was 28.8 months for vascular studies and 45.3 months for motor, sensory, and QuickDASH evaluations. Although mid and distal radial artery flow velocities were significantly higher in donor versus control extremities evaluated at less than 1 year postoperatively, there was no significant difference in extremities evaluated at later time points. Digital pressures, grip strength, key pinch strength, and ulnar sensation were equivalent between donor and control extremities. The mean QuickDASH score was 17.4 ± 23.8. The UFF can be harvested reliably and long-term follow-up shows no evidence of impaired vascular, motor, or sensory function in the donor extremity.

Revisiting the anatomic relationship of the marginal mandibular nerve and the posterior facial vein: a cadaveric study.

In preparation for the donor and recipient facial vascularized composite allotransplant (VCA), the marginal mandibular nerve branch should be identified and co-apted to the recipient's nerve to allow for re-innervation. We describe a method to identify the marginal mandibular branch of the facial nerve in facial VCA donors and recipients. Through cadaver dissections, the posterior facial vein was traced posteriorly to identify the marginal mandibular branch of the facial nerve. In cases where we were unable to use this relationship, we found the posterior facial venous system to be diminutive. This technique is useful for finding the marginal mandibular branch when dissecting anterograde to the parotid gland.

Engineering bone grafts with enhanced bone marrow and native scaffolds.

The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds.

Regulatory T cells are not predictive of outcomes in a nonhuman primate model of vascularized composite allotransplantation.

BACKGROUND: T regulatory cells (Tregs) have been associated with prolonged allograft survival and tolerance across a wide variety of species and organ types. We used our nonhuman primate model of facial vascularized composite allotransplantation (VCA) to study the association of Tregs with graft outcomes. METHODS: We quantified Tregs in peripheral blood and allograft biopsies from nonhuman primates after heterotopic partial facial segment allotransplantation from major histocompatibility complex class I-mismatched donors using flow cytometry and immunohistochemistry. Immunosuppression consisted of tacrolimus and mycophenolate mofetil without induction or depletional therapies. Circulating and graft skin Treg values were compared with graft outcomes and with histologic grade from concurrent biopsies. RESULTS: Treg proportion in peripheral blood ranged from 0.156% to 9.00% with a mean of 3.34%±0.22%. FoxP3 staining was observed in 3 of 29 graft biopsies. Median circulating Treg value did not predict time to Banff grade II rejection (hazard ratio, 0.9; confidence interval, 0.4-2.2) or graft loss (hazard ratio, 0.5; confidence interval, 0.01-5.3). Animals that experienced rejection did not have significantly different peripheral blood or graft skin Treg values from those that did not. Biopsy specimens with grade I or II rejection were more likely to contain Tregs (25% vs. 0%; P=0.044) despite no difference in concurrent circulating Tregs (3.56% vs. 3.36%; P=0.704). CONCLUSIONS: These findings in a clinically relevant model suggest that Tregs may have limited prognostic value with standard immunosuppressive protocols used in VCA. Further studies are necessary to determine the specific role of Tregs in VCA and any role of Treg monitoring in clinical practice.

Surface anatomy of the middle division of the facial nerve: Zuker's point.

BACKGROUND: The anatomy of the facial nerve and its branches has been well documented. The course of the extratemporal facial nerve, its anatomical planes, and the surface landmarks of the temporal division and marginal mandibular division are well known. However, the surface landmark of the middle division of the facial nerve has not been studied to date. METHODS: Eighteen hemifacial dissections in 10 fresh human cadavers were performed through a preauricular face-lift incision. An 18-gauge needle with brilliant green dye was used to mark the nerve through the skin before dissection. The exact location of the middle division branches of the facial nerve was documented in relation to the transcutaneous marking. RESULTS: The middle division branches of the facial nerve were found to lie at a mean of 2.3 mm from the tattooed point, with a range of 0 to 6 mm. A nerve branch was found directly tattooed by the needle seven of 18 times, inferior to the tattoo five of 18 times, and superior to the tattoo six of 18 times. CONCLUSIONS: The zygomatic/buccal motor branch that innervates the zygomaticus major muscle can be reliably found at the midway point on a line drawn from the root of the helix and the lateral commissure of the mouth. This study will help guide surgeons to the middle division of the facial nerve as it applies to facial surgery.

Frontal sinus mucocele development in an adult patient with Apert syndrome.

Frontal sinus mucoceles may present many years after traumatic injuries or surgical procedures involving the frontal bone, but have been rarely reported after fronto-orbital advancement. We describe a case of frontal sinus mucocele development in a 43-year-old patient with Apert syndrome who underwent fronto-orbital advancement as a child. This was treated with resection and free fibula osteomuscular flap reconstruction. Computer-aided design and manufacturing techniques were used to virtually plan the procedure and guide the osteotomies intraoperatively. Follow-up at 1 year postoperatively revealed no evidence of recurrence.

Total face, double jaw, and tongue transplantation: an evolutionary concept.

BACKGROUND: The central face high-energy avulsive injury has been frequently encountered and predictably managed at the R Adams Cowley Shock Trauma Center. However, despite significant surgical advances and multiple surgical procedures, the ultimate outcome continues to reveal an inanimate, insensate, and suboptimal aesthetic result. METHODS: To effectively address this challenging deformity, a comprehensive multidisciplinary approach was devised. The strategy involved the foundation of a basic science laboratory, the cultivation of a supportive institutional clinical environment, the innovative application of technologies, cadaveric simulations, a real-time clinical rehearsal, and an informed and willing recipient who had the characteristic deformity. RESULTS: After institutional review board and organ procurement organization approval, a total face, double jaw, and tongue transplantation was performed on a 37-year-old man with a central face high-energy avulsive ballistic injury. CONCLUSIONS: This facial transplant represents the most comprehensive transplant performed to date. Through a systematic approach and clinical adherence to fundamental principles of aesthetic surgery, craniofacial surgery, and microsurgery and the innovative application of technologies, restoration of human appearance and function for individuals with a devastating composite disfigurement is now a reality. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Total face, double jaw, and tongue transplant simulation: a cadaveric study using computer-assisted techniques.

BACKGROUND: With the transplantation of more extensive facial vascularized composite allografts, fundamental craniofacial and aesthetic principles become increasingly important. In addition, computer-assisted planning and intraoperative navigation may improve precision and efficiency in these complex procedures. METHODS: Ten mock face transplants were performed in 20 cadavers. The vascularized composite allograft consisted of all facial skin, mimetic muscles, the tongue, the midface by means of a Le Fort III osteotomy, and the mandible by means of sagittal split osteotomies. Craniofacial computed tomographic scans were obtained before and after the mock transplants. Surgical planning software was used to virtually plan the osteotomies, and a surgical navigation system guided the osteotomies intraoperatively. Cephalometric analyses were compared between the virtually planned transplants and the actual postoperative results. RESULTS: The combination of preoperative computerized planning and intraoperative guidance consistently produced a vascularized composite allograft that could be easily fixated to the prepared recipient, with only minimal burring of osteotomy sites necessary. Satisfactory occlusion was maintained, and postoperative computed tomography confirmed accurate skeletal fixation. Insignificant differences with regard to cephalometric analyses were noted when predicted and actual postoperative data were compared. CONCLUSIONS: The authors' experience treating severe craniofacial injury allowed consistent transfer of facial vascularized composite allografts, maintaining proper occlusion. Preoperative computer planning and intraoperative navigation ensured precise osteotomies and a good donor-recipient skeletal match, which greatly reduced the need for intraoperative adjustments and manipulation. This total facial vascularized composite allograft represents one of the most extensive described and is intended to represent a typical central facial demolition pattern.

Total face, double jaw, and tongue transplant research procurement: an educational model.

BACKGROUND: Transplantation of a facial vascularized composite allograft is a highly complex procedure that requires meticulous planning and affords little room for error. Although cadaveric dissections are an essential preparatory exercise, they cannot simulate the true clinical experience of facial vascularized composite allograft recovery. METHODS: After obtaining institutional review board approval to perform a facial vascularized composite allograft research procurement, a 66-year-old, brain-dead donor was identified. The family graciously consented to donation of a total face, double jaw, and tongue allograft and multiple solid organs. RESULTS: A craniofacial computed tomographic angiogram was obtained preoperatively to define the vascular anatomy and facilitate virtual computerized surgical planning. The allograft was procured in 10 hours, with an additional 2 hours required for an open tracheostomy and silicone facial impression. The donor was coagulopathic throughout the recovery, resulting in an estimated blood loss of 1500 ml. Fluorescence angiography confirmed adequate perfusion of the entire allograft based on lingual and facial arterial and external jugular and thyrolinguofacial venous pedicles. The solid organ transplant team initiated abdominal organ isolation while the facial allograft procurement was in progress. After completion of allograft recovery, the kidneys and liver were recovered without complication. CONCLUSIONS: Before conducting a clinical face transplant, adequate preparation is critical to maximize vascularized composite allotransplantation outcomes and preserve solid organ allograft function. As more centers begin to perform facial transplantation, research procurement of a facial vascularized composite allograft offers a unique educational opportunity for the surgical and anesthesia teams, the organ procurement organization, and the institution.

Flexor pollicis longus tendon rupture after volar plating of a distal radius fracture: pronator quadratus plate coverage may not adequately protect tendons.

OBJECTIVE: The senior author previously reported a case of rupture of the flexor policis longus tendon after volar plating of a distal radius fracture. We hypothesized that restoration of the pronator quadratus to its native position after plating might prevent this problem. METHODS: The authors report a new case of irritation of the flexor policis longus 2.5 years after volar plating of a distal radius fracture. The plate was in good contact with the bone, and the pronator quadratus had been restored to its native position. Despite this, there was a partial-thickness laceration of the tendon over the plate and a defect in the pronator quadratus muscle which had been between the plate and the tendon. RESULTS: The patient was treated with removal of the plate and repair of the tendon. She never lost function of the flexor policis longus tendon and has full function of her hand. CONCLUSIONS: The authors believe that restoration of the pronator quadratus to its native position after volar plating of a distal radius fracture does protect the overlying flexor tendons. Even with this step, tendon irritation can still occur. The authors advise their patients at the time of discharge from initial treatment of their distal radius fracture to be vigilant for any evidence of flexor tendon irritation and to return for evaluation if they have any suspicion of this.

Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema.

Rtp801 (also known as Redd1, and encoded by Ddit4), a stress-related protein triggered by adverse environmental conditions, inhibits mammalian target of rapamycin (mTOR) by stabilizing the TSC1-TSC2 inhibitory complex and enhances oxidative stress-dependent cell death. We postulated that Rtp801 acts as a potential amplifying switch in the development of cigarette smoke-induced lung injury, leading to emphysema. Rtp801 mRNA and protein were overexpressed in human emphysematous lungs and in lungs of mice exposed to cigarette smoke. The regulation of Rtp801 expression by cigarette smoke may rely on oxidative stress-dependent activation of the CCAAT response element in its promoter. We also found that Rtp801 was necessary and sufficient for nuclear factor-kappaB (NF-kappaB) activation in cultured cells and, when forcefully expressed in mouse lungs, it promoted NF-kappaB activation, alveolar inflammation, oxidative stress and apoptosis of alveolar septal cells. In contrast, Rtp801 knockout mice were markedly protected against acute cigarette smoke-induced lung injury, partly via increased mTOR signaling, and, when exposed chronically to cigarette smoke, against emphysema. Our data support the notion that Rtp801 may represent a major molecular sensor and mediator of cigarette smoke-induced lung injury.