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  1. Dai J, Alvarado R, Ali S, Ahmed Z, Meo MS
    Environ Sci Pollut Res Int, 2023 Mar;30(14):40094-40106.
    PMID: 36607580 DOI: 10.1007/s11356-022-25100-3
    Attaining Sustainable Development Goals (SDGs) is important to control the adverse impacts of climate change and achieve sustainable development. Among the 17 SDGs, target 13 emphasizes enhancing urgent actions to combat climate-related changes. This target is also dependent on target 7, which advocates enhancing access to cheap alternative sustainable energy. To accomplish these targets, it is vital to curb the transport CO2 emissions (TCO2) which increased by approximately 80% from 1990 to 2019. Thus, this study assesses the role of transport renewable energy consumption (TRN) in TCO2 by taking into consideration transport fossil fuel consumption (TTF) and road infrastructure (RF) from 1970 to 2019 for the United States (US) with the intention to suggest some suitable mitigation policies. Also, this study assessed the presence of transport environmental Kuznets curve (EKC) to assess the direction of transport-induced growth. The study used the Bayer-Hanck cointegration test which utilizes four different cointegration techniques to decide cointegration along with the Gradual Shift causality test which considers structural shift and fractional integration in time series data. The long-run findings of the Dynamic Ordinary Least Squares (DOLS) test, which counters endogeneity and serial correlation, revealed that the transport renewable energy use mitigates as well as Granger causes TCO2. However, transport fossil fuel usage and road infrastructure enhance TCO2. Surprisingly, the transport EKC is invalid in the case of the US, and increased growth levels are harmful to the environment. The association between TCO2 and economic growth is similar to a U-shaped curve. The Spectral Causality test revealed the growth hypothesis regarding transport fossil fuel use and economic growth connection, which suggests that policymakers should be cautious while decreasing the usage of transport fossil fuels because it may hamper economic progress. These findings call for revisiting growth strategies and increasing green energy utilization in the transport sector to mitigate transport emissions.
  2. Hamizan AW, Rimmer J, Alvarado R, Sewell WA, Tatersall J, Barham HP, et al.
    Am J Rhinol Allergy, 2019 Mar;33(2):178-183.
    PMID: 30656948 DOI: 10.1177/1945892418825224
    BACKGROUND: Specific immunoglobulin E (sIgE) within the nasal airway is likely to be the most ideal marker of allergic status, but little is known of the normative values in asymptomatic patients and those with rhinitis.

    OBJECTIVE: The aim of this study was to assess the diagnostic characteristics of inferior turbinate tissue biopsy sIgE in asymptomatic and rhinitic patients.

    METHODS: A diagnostic cross-sectional study was undertaken, involving patients who underwent inferior turbinate surgery with or without other surgical interventions. Inferior turbinate tissue biopsy was performed during surgery and was assessed for allergen sIgE (dust mite, grass [temperate or subtropical], and animal epithelium) using an automated immunoassay. Tissue sIgE was assessed among asymptomatic patients and those with nasal symptoms. Data were presented as median (interquartile range). A receiver operating curve was used to predict the diagnostic utility of turbinate tissue sIgE in determining allergic rhinitis.

    RESULTS: A total of 160 patients (41.89 ± 14.65 years, 36.9% females) were included. The median tissue sIgE concentration among the asymptomatic nonatopic group of patients was 0.09 (0.08-0.10) kUA/L and tissue sIgE > 0.10 kUA/L was determined as a positive threshold. Inferior turbinate tissue sIgE was shown to be a predictive test for allergic rhinitis (area under curve: 0.87, 95% confidence interval: 0.84-0.90) with 90% sensitivity and 89% negative predictive value.

    CONCLUSION: Inferior turbinate tissue biopsy sIgE is a sensitive tool to predict allergic rhinitis. The threshold value of 0.1 kUA/L corresponded well with the asymptomatic nonatopic group of patients. This method detects sIgE in the nasal mucosa and may be a useful test for allergic rhinitis in future research.

  3. Hamizan AW, Loftus PA, Alvarado R, Ho J, Kalish L, Sacks R, et al.
    Laryngoscope, 2018 09;128(9):2015-2021.
    PMID: 29602169 DOI: 10.1002/lary.27180
    OBJECTIVES/HYPOTHESIS: Polypoid edema of the middle turbinate is a marker of inhalant allergy. Extensive edematous changes may result in limited central nasal and sinus disease, which has been called central compartment atopic disease (CCAD). Radiologically, this is seen as soft tissue thickening in the central portion of the sinonasal cavity with or without paranasal sinus involvement. When the sinuses are involved, the soft tissue thickening spares the sinus roof or lateral wall (centrally limited). This centrally limited radiological pattern was assessed among chronic rhinosinusitis (CRS) patients and compared to allergy status.

    STUDY DESIGN: Diagnostic cross-sectional study.

    METHODS: This study included consecutive CRS patients without prior sinus surgery. Computed tomography (CT) scans of the paranasal sinuses were blindly assessed and allergy status was confirmed by serum or skin testing. Individual sinus cavities were defined as either centrally limited or diffuse disease. The radiological pattern that may predict allergy was determined, and its diagnostic accuracy was calculated.

    RESULTS: One hundred twelve patients diagnosed to have CRS, representing 224 sides, were assessed (age 46.31 ± 13.57 years, 38.39% female, 41.07% asthma, Lund-Mackay CT score 15.88 ± 4.35, 56.25% atopic). The radiological pattern defined by centrally limited changes in all of the paranasal sinuses was associated with allergy status (73.53% vs. 53.16%, P = .03). This predicted atopy with 90.82% specificity, 73.53% positive predictive value, likelihood positive ratios of 2.16, and diagnostic odds ratio of 4.59.

    CONCLUSIONS: A central radiological pattern of mucosal disease is associated with inhalant allergen sensitization. This group may represent a CCAD subgroup of patients with mainly allergic etiology.

    LEVEL OF EVIDENCE: 3b Laryngoscope, 128:2015-2021, 2018.

  4. Saricilar EC, Hamizan A, Alvarado R, Rimmer J, Sewell W, Tatersall J, et al.
    Am J Rhinol Allergy, 2018 Jul;32(4):244-251.
    PMID: 29785855 DOI: 10.1177/1945892418777668
    Background Rhinitis is a highly prevalent yet often misdiagnosed condition. Patients who have local allergic rhinitis are regularly mislabeled as having a nonallergic etiology. Thus, a highly accurate, reproducible, and noninvasive assessment, which can be performed quickly and with minimal discomfort to the patient, is required. Objective The aim of this research was to identify the efficiency of various nasal brushes as tools for harvest and collection of epithelial proteins and its suitability for identification of rhinitis. Methods Nasal epithelial mucosa samples were taken from patients undergoing turbinate surgery using a cytology brush, a dental brush, and a nasal curette in random order. After washing in phosphate-buffered saline, the suspended cells were sonicated. Total protein content was assessed for all samples by bicinchoninic acid assay measured using a Nanodrop machine. Identification of nasal-specific immunoglobulin E (spIgE) was then assessed using immunoassay and compared to the patient's allergic status from epicutaneous and serum testing. The lower threshold limit for the spIgE in nasal brushings was determined using the results of serum spIgE tests as the reference. The diagnostic accuracy of this new established cutoff value was determined. Results The cytology brush was found to be the optimal tool for maximal nasal mucosa protein collection followed by dental brush and nasal curette (0.75 ± 0.45 mg/mL vs 0.43 ± 0.24 mg/mL vs 0.071 ± 0.55 mg/mL, respectively; P 
  5. Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ
    Am J Rhinol Allergy, 2018 Jul;32(4):252-257.
    PMID: 29862828 DOI: 10.1177/1945892418779451
    Background Eosinophilic chronic rhinosinusitis (eCRS) is linked with skewed T-helper 2 or immunoglobulin E (IgE)-mediated allergic responses, with differing diagnosis, prognosis, and management to non-eCRS. Objective The association between biomarkers and eCRS was investigated to assess the predictors of eCRS. Methods A cross-sectional study of adult patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery was conducted. eCRS was defined by histopathological assessment showing >10 eosinophils/high-power field on sinus mucosal biopsy. Blood tests were performed preoperatively and assessed for a full blood count including eosinophils and a white cell count (WCC) as well as biochemical markers of inflammation and atopy including Immunoglobulin E (IgE), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ImmunoCAP testing for serum-specific IgE. Comparisons between eCRS and non-eCRS patients were performed. Results 345 patients (48.1% female, age 48.72 ± 15.06 years) were recruited, with 206 (59.7%) identified as eCRS, 41% with asthma and 47% CRS with nasal polyps. eCRS patients were more likely to have asthma ( P 0.24 × 109/L), eosinophil ratio (>4.27% of total WCC), and lower ESR when compared with non-eCRS.
  6. Hamizan AW, Rimmer J, Alvarado R, Sewell WA, Kalish L, Sacks R, et al.
    Int Forum Allergy Rhinol, 2017 09;7(9):868-877.
    PMID: 28727909 DOI: 10.1002/alr.21988
    BACKGROUND: The diagnosis of allergic rhinitis (AR) is based on cutaneous and serological assessment to determine immunoglobulin E (IgE)-mediated disease. However, discrepancies between these tests and nasal provocation exist. Patients diagnosed as non-allergic rhinitis (NAR) but with positive nasal allergen provocation test (NAPT) may represent a local allergic condition or entopy, still suitable to allergy interventions. The objective of this study was to determine the frequency of nasal reactivity toward allergens among AR and NAR patients, and to describe the diagnostic characteristics of NAPT methodologies.

    METHODS: EMBASE (1947-) and Medline (1946-) were searched until December 8, 2015. A search strategy was used to identify studies on AR or NAR patients subjected to diagnostic local nasal provocation. All studies providing original NAPT data among the AR or NAR population were included. Meta-analysis of proportion data was presented as a weighted probability % (95% confidence interval [CI]).

    RESULTS: The search yielded 4504 studies and 46 were included. The probability of nasal allergen reactivity for the AR population was 86.3% (95% CI, 84.4 to 88.1) and in NAR was 24.7% (95% CI, 22.3 to 27.2). Reactivity was high with pollen for both AR 97.1% (95% CI, 94.2 to 99.2) and NAR 47.5% (95% CI, 34.8 to 60.4), and lowest with dust for both AR 79.1% (95% CI, 76.4 to 81.6) and NAR 12.2% (95% CI, 9.9 to 14.7). NAPT yielded high positivity when defined by subjective end-points: AR 91.0% (95% CI, 86.6 to 94.8) and NAR 30.2% (95% CI, 22.9 to 37.9); and lower with objective end-points: AR 80.8% (95% CI, 76.8 to 84.5) and NAR 14.1% (95% CI, 11.2 to 17.2).

    CONCLUSION: Local allergen reactivity is demonstrated in 26.5% of patients previously considered non-allergic. Similarly, AR, when defined by skin-prick test (SPT) or serum specific IgE (sIgE), may lead to 13.7% of patients with inaccurate allergen sensitization or non-allergic etiologies.

  7. Wong E, Hamizan AW, Alvarado R, Orgain CA, Kalish L, Sacks R, et al.
    Am J Otolaryngol, 2018 06 22;39(5):570-574.
    PMID: 29961655 DOI: 10.1016/j.amjoto.2018.06.019
    PURPOSE: Middle turbinate head edema has recently been found to have high specificity for diagnosis of inhalant allergy. However, subtle mucosal edema can be difficult to appreciate under white light endoscopy. Narrow band imaging (NBI) has the potential to demonstrate edema by identifying reduced mucosal vascularity and improve sensitivity for the detection of mucosal edema. Narrow band imaging was assessed to determine its utility in objectifying mucosal edema.

    MEATERIALS AND METHODS: A cross-sectional diagnostic study was performed on patients with edematous mucosa of the middle turbinate head. Under traditional white light endoscopy, areas of edematous mucosa were identified. Using NBI, these areas were compared to areas of normal mucosa on the middle turbinate head. NBI images of these same areas were then converted to grey scale and a vascularity index was created by pixel analysis and brightness in Fiji Image J software (Wisconsin, US).

    RESULTS: Thirty-three middle turbinates were assessed (age 42.4 ± 12.5, 42.4% female). NBI discriminated between areas identified under white light endoscopy as edematous and normal (158.2 ± 48.4 v 96.9 ± 32.7 p 

  8. Hamizan AW, Rimmer J, Husain S, Alvarado R, Tatersall J, Sewell W, et al.
    Rhinology, 2019 Feb 01;57(1):10-20.
    PMID: 30219822 DOI: 10.4193/Rhin18.074
    BACKGROUND: Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to summarize the studies which reported the presence of nspIgE among patients diagnosed as NAR.

    METHODS: Embase (1947- ) and Medline (1946-) were searched until 6th June 2017. A search strategy was utilized to identify studies on nspIgE among patients with NAR. The target population was patients with symptoms of rhinitis, but negative systemic allergen sensitization. Studies with original data on detectable nspIgE among the NAR population were included. Meta-analysis of single proportions as a weighted probability %(95%CI) was performed. Heterogeneity was explored amongst studies.

    RESULTS: A search strategy returned 2286 studies and 21 were included. These studies involved 648 participants with NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on studies with nasal secretions. The weighted proportion of detectable nspIgE in nasal secretions within patients with NAR was 10.2 (7.4-13.4) %. Population definitions partly explained variability. Detection of nspIgE was lower in patients without a history suggestive of allergy compared to those with a positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01).

    CONCLUSION: NAR with positive allergy history suggests presence of nspIgE. These patients warrant further allergology evaluation to confirm localized nasal allergy, as they benefit from allergy therapy such as immunotherapy.

  9. Bulut U, Ongan S, Dogru T, Işık C, Ahmad M, Alvarado R, et al.
    Environ Sci Pollut Res Int, 2023 Aug;30(36):86138-86154.
    PMID: 37400702 DOI: 10.1007/s11356-023-28319-w
    This study examines the impact of government spending, income, and tourism consumption on CO2 emissions in the 50 US states through a novel theoretical model derived from the Armey Curve model and the Environmental Kuznets Curve hypothesis. The findings of this research are essential for policymakers to develop effective strategies for mitigating environmental pollution. Utilizing panel cointegration analysis, the study provides valuable insights into whether continued increases in government spending contribute to higher pollution levels. By identifying the threshold point of spending as a percentage of GDP, policymakers can make informed decisions to avoid the trade-off between increased spending and environmental degradation. For instance, the analysis reveals that Hawaii's tipping point is 16.40%. The empirical results underscore the importance of adopting sustainable policies that foster economic growth while minimizing environmental harm. These findings will aid policymakers in formulating targeted and efficient approaches to tackle climate change and promote long-term environmental sustainability in the United States. Moreover, the impact of tourism development on CO2 emissions varies across states, with some US states experiencing a decrease while others see an increase.
  10. Mo S, Gupta SS, Stroud A, Strazdins E, Hamizan AW, Rimmer J, et al.
    Laryngoscope, 2021 02;131(2):260-267.
    PMID: 32386248 DOI: 10.1002/lary.28682
    OBJECTIVES: Nasal peak inspiratory flow (NPIF) is a practical and affordable tool that measures maximum inspiratory flow rate through both nostrils. Although NPIF values for healthy controls and patients appear to differ considerably, a generally expected value for populations with and without nasal obstruction has yet to be established. The aim of this systematic review and meta-analysis was to determine the mean NPIF value in populations with and without nasal obstruction.

    METHODS: Medline (1946-) and Embase (1947-) were searched until July 1, 2017. A search strategy was used to identify studies that reported NPIF values for defined healthy or disease states. All studies providing original data were included. The study population was defined as having either normal nasal breathing or nasal obstruction. A meta-analysis of the mean data was presented in forest plots, and data were presented as mean (95% confidence interval [CI]).

    RESULTS: The search yielded 1,526 studies, of which 29 were included. The included studies involved 1,634 subjects with normal nasal breathing and 817 subjects with nasal obstruction. The mean NPIF value for populations with normal nasal breathing was 138.4 (95% CI: 127.9-148.8) L/min. The mean value for populations with nasal obstruction was 97.5 (95% CI: 86.1-108.8) L/min.

    CONCLUSIONS: Current evidence confirms a difference between mean NPIF values of populations with and without nasal obstruction. The mean value of subjects with no nasal obstruction is 138.4 L/min, and the mean value of nasally obstructed populations is 97.5 L/min. Prospective studies adopting a standardized procedure are required to further assess normative NPIF values. Laryngoscope, 131:260-267, 2021.

  11. Stroud A, Dhaliwal P, Alvarado R, Winder MJ, Jonker BP, Grayson JW, et al.
    Pituitary, 2020 Oct;23(5):595-609.
    PMID: 32691356 DOI: 10.1007/s11102-020-01066-8
    PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes.

    METHODS: Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size 

  12. Hamizan AW, Azer M, Alvarado R, Earls P, Barham HP, Tattersall J, et al.
    Am J Rhinol Allergy, 2019 Sep;33(5):524-530.
    PMID: 31106562 DOI: 10.1177/1945892419850750
  13. Hamizan AW, Alvarado R, Arifin KT, Zahedi FD, Sian NC, Jumaat AF, et al.
    PMID: 37061936 DOI: 10.12932/AP-031122-1495
    BACKGROUND: Skin prick testing and serological identification of allergen specific immunoglobulin E (spIgE) are standard tests for allergic rhinitis but can only identify systemic responses. In contrast, nasal allergen challenge (NAC), directly assess localized nasal mucosal reactivity, but is time consuming. Identification of spIgE from nasal brushings (nasal spIgE) is an alternative technique.

    OBJECTIVE: This study aimed to determine the diagnostic performance of nasal spIgE compared to NAC in order predict house dust mite (HDM) driven AR.

    METHODS: A diagnostic cross-sectional study involving adult rhinitis patients was performed. Sensitization to HDM allergens (Dermatophagoides pteronyssinus (DP), Dermatophagoides farina (DF) were assessed serologically and/or skin prick test, nasal brushing and NAC. Patients with both positive systemic test and NAC were defined to have HDM driven AR, while patients with a positive systemic test and negative NAC were defined to have non-clinically relevant HDM sensitization. The performance of nasal spIgE to predict positive NAC was determined using the receiver operating curve. The chosen cut-off was then used to predict HDM driven AR among those with positive systemic test.

    RESULTS: 118 patients (29.42 ± 9.32 years, 61.9% female) were included. Nasal spIgE was predictive of positive NAC (AUC 0.93, 95%CI: 0.88-0.98, p < 0.01). Among those with positive systemic test, the cut-off value of >0.14 kUA/L was able to predict HDM AR from incidental HDM sensitization with 92% sensitivity and 86% specificity.

    CONCLUSIONS: Nasal spIgE is comparable to NAC. A cut-off value of >0.14 kUA/L identifies HDM-driven AR from incidental sensitization among patients with positive systemic tests for allergy.

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