The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience exacerbations more frequently than those with asthma or COPD alone. Since low diffusing capacity of the lung for carbon monoxide (DLCO) is known as a strong risk factor for severe exacerbation in COPD, DLCO or a transfer coefficient of the lung for carbon monoxide (KCO) is speculated to also be associated with the risk of exacerbations in ACO. METHODS: This study was conducted as an observational cohort survey at the National Hospital Organization Fukuoka National Hospital. DLCO and KCO were measured in 94 patients aged ≥ 40 years with a confirmed diagnosis of ACO. Multivariable-adjusted hazard ratios (HRs) for the exacerbation-free rate over one year were estimated and compared across the levels of DLCO and KCO. RESULTS: Within one year, 33.3% of the cohort experienced exacerbations. After adjustment for potential confounders, low KCO (< 80% per predicted) was positively associated with the incidence of exacerbation (multivariable-adjusted HR = 3.71 (95% confidence interval 1.32-10.4)). The association between low DLCO (< 80% per predicted) and exacerbations showed similar trends, although it failed to reach statistical significance (multivariable-adjusted HR = 1.31 (95% confidence interval 0.55-3.11)). CONCLUSIONS: Low KCO was a significant risk factor for exacerbations among patients with ACO. Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory.

Association of serum antibodies against the Mycobacterium avium complex and hemoptysis: a cross-sectional study.

BACKGROUND: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. METHODS: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. To investigate the linear trends in the relationship between MAC-Ab levels and hemoptysis, the subjects were classified into three groups using the tertile distribution of the MAC-Ab. RESULTS: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2 and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15-7.44)). Likewise, when categorizing the subjects into three groups, the risk of hemoptysis increased with increasing MAC-Ab levels (P = 0.03 for trend). CONCLUSIONS: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. There were also positive trends in the association between the MAC-Ab titer and the likelihood of hemoptysis. Measuring the MAC-Ab may contribute not only to early detection of the risk of hemoptysis but also to early intervention with anti-NTM therapy and, as a result, to the prevention of hemoptysis in MAC patients.

Centrifugation-Controlled Thermal Convection and Its Application to Rapid Microfluidic Polymerase Chain Reaction Devices.

Here, we report the developed cyclo olefin polymer (COP) microfluidic chip on a fabricated rotating heater stage that utilizes centrifugation-assisted thermal cycle in a ring-structured microchannel for polymerase chain reaction (PCR). The PCR solution could be driven by thermal convection and continuously exchanged high/low temperatures in a ring structured microchannel without the use of typical syringe pump. More importantly, the flow rate was controlled by the relative gravitational acceleration only. The platform enables amplification within 10 min at 5G and has a detection limit of 70.5 pg/channel DNA concentration (ß-actin, 295 bp). The current rotating system is capable of testing four different samples in parallel. The microfluidic chip can be preloaded with the PCR premix solution for on-site utility, and, with all of the features integrated to the system, the test can be conducted without the need for specialized laboratory and trained laboratory staff. In addition, this innovative chemical reaction technique has the potential to be utilized in other micromixing applications.

Histamine H1 and H4 receptor expression on the ocular surface of patients with chronic allergic conjunctival diseases.

BACKGROUND: This study investigated the histamine H1 and H4 receptors mRNA (H1R and H4R, respectively) expression on the ocular surface of patients with chronic forms of allergic conjunctival diseases to determine whether they can serve as biomarkers for allergic inflammation in the conjunctiva. METHODS: We examined 19 patients with vernal or atopic keratoconjunctivitis (AKC/VKC group) and 15 healthy volunteers (control group). The AKC/VKC group was divided into active and stable stage subgroups. Specimens were obtained from the upper tarsal conjunctiva of each participant using a modified impression cytology method. H1R, H4R, and eotaxin-1, -2, and -3 mRNA (eotaxin-1, eotaxin-2, eotaxin-3, respectively) expression was determined by real-time RT-PCR. Immunohistochemical analysis for eosinophil cationic protein (ECP), eosinophil major basic protein (MBP), eotaxin-2, and histamine H4 receptor (H4R) were performed using conjunctival smears. RESULTS: The number of H4R-positive patients was higher in the active than the stable stage subgroup and control group, whereas no difference was observed for H1R. H1R levels were higher in the active than in the stable stage subgroup, while those of H4R were higher in the active stage subgroup than in the control group. H1R and H4R levels were correlated with eotaxin-2 level. In immunohistochemical analysis, H4R revealed their expression on eosinophils in conjunctival smears of patients with AKC/VKC. CONCLUSIONS: H4R is useful as biomarkers of allergic inflammation on ocular surfaces. Most notably, H4R expressed on eosinophils is useful as a biomarker of eosinophilic inflammation of the ocular surface.

Impairment of flicker-induced increase in retinal blood flow in diabetic pigs.

PURPOSE: To evaluate retinal blood flow (RBF) regulation in response to RBF stress in maturity-onset diabetes of the young type 3 (MODY3) pigs. STUDY DESIGN: Case-control study. METHODS: MODY3 pigs (diabetes mellitus [DM] group, n = 8) transfected with the human mutant hepatocyte nuclear factor-1⍺ and normal pigs of the same age (normal group, n = 8) were used as subjects. After confirming DM onset, the experiment was performed under inhalation anesthesia with isoflurane at 2 months of age before the cataract progressed. Ocular blood flow was assessed by calculating the optic papillary mean blur rate using laser speckle flowgraphy, modified for pig eye measurements. After baseline ocular blood flow measurements, flicker stimulation (12 Hz, 3 min) was applied, and ocular blood flow was measured over time. RESULTS: Blood glucose was 81.8 ± 5.1 mg/dL in the normal group and 311.4 ± 23.1 mg/dL in the DM group (mean ± standard error). The percent change in ocular blood flow at 3 min after flicker stimulation was +31.0 ± 10.9% in the normal group and -6.6 ± 6.5% in the DM group compared to the preload value, and the difference was statistically significant (Mann-Whitney test, P = 0.015). CONCLUSION: RBF response to flicker stimulation is reduced at 2 months of age in MODY3 pigs, suggesting that retinal neurovascular coupling is impaired from the early onset of DM.

Comparison of Postoperative Stability of Intraocular Lenses after Phacovitrectomy for Rhegmatogenous Retinal Detachment.

We retrospectively compared the stability of intraocular lenses (IOLs) routinely used at our institution by measuring IOL position after phacovitrectomy for rhegmatogenous retinal detachment (RRD). Patients with RRD who underwent phacovitrectomy with gas tamponade received one of three IOLs: 6-mm, single-piece NS-60YG (NIDEK, 15 eyes); 6-mm, single-piece XY1 (HOYA, 11 eyes); or 7-mm, three-piece X-70 (Santen, 11 eyes). Various parameters associated with the anterior chamber, lens, and IOL were measured by swept-source anterior segment optical coherence tomography (CASIA2; Tomey Corp) before and 1 week and 1 month after surgery. IOL position was determined as follows: IOL position = (postoperative aqueous depth [AQD] − preoperative AQD)/lens thickness. We found no significant difference in axial length between the IOLs (p = 0.97). At 1 week, IOL position was as follows: NS-60YG, 0.32; XY1, 0.24; and X-70, 0.26 (p < 0.05). The respective IOL positions at 1 month were 0.35, 0.27, and 0.28 (p < 0.01). These results indicated the smallest anterior shift with NS-60YG. To replicate the anterior shift of IOL position ex vivo, biomechanical measurement was performed. NS-60YG resisted more displacement force than the other IOLs. Thus, in eyes undergoing phacovitrectomy for RRD, NS-60YG was the most stable of the three IOLs studied.

The kebab technique uses a bipolar pencil to retrieve a dropped nucleus of the lens via a small incision.

We developed a new method to retrieve a dropped nucleus of the lens via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus of the lens was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean (standard deviation, SD) 1.67 logMAR (0.90) to 1.14 logMAR (1.01). The mean preoperative IOP was 24.5 (16.8) mmHg and postoperative IOP was 11.0 (2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (431) cells/mm2. There were no postoperative complications. The retrieval of a dropped nucleus of the lens using a bipolar pencil enables small incisions without using PFCL.

Evaluation of ocular blood flow over time in a treated retinal arterial macroaneurysm using laser speckle flowgraphy.

PURPOSE: To report the changes over time in ocular blood flow quantified by laser speckle flowgraphy (LSFG) in a treated large retinal arterial macroaneurysm (RAM). OBSERVATIONS: A 72-year old female presented with sudden decreased vision in the left eye. Fundus examination revealed a RAM and vitreous hemorrhage (VH), which worsened over one month. A vitrectomy was performed to remove the VH, with 20% sulfur hexafluoride injected into the vitreous cavity. The VH recurred two weeks later and the RAM was found to have enlarged from one-quarter disc diameter (DD) to three DDs during a second vitrectomy. The RAM subsequently shrunk spontaneously to one DD without recurrent VH during the following 2 weeks. Beginning 4 weeks after the second vitrectomy we performed serial LSFG examinations of the RAM and found that the mean blur rate (MBR) of the RAM and retinal flow volume (RFV) in both the feeding arteriole and draining venule decreased as the RAM continued to involute. CONCLUSIONS AND IMPORTANCE: MBR and arteriolar and venular RFV measured by LSFG decreased with RAM involution. Longitudinal followup of blood flow by LSFG may be useful for noninvasive evaluation of the stability of RAMs.

Development of Stage 4 Macular Hole after Spontaneous Closure in a Patient with Stage 2 Macular Hole and a Lamellar Macular Hole-Associated Epiretinal Proliferation.

Herein, we report the longitudinal observation of a case with reopening of the macular hole associated with a lamellar macular hole-associated epiretinal proliferation (LHEP) followed by spontaneous closure in patients with stage 2 idiopathic macular hole. A 64-year-old woman was referred for the decreased visual acuity (VA) and acute anorthopia in the right eye. Funduscopy and optical coherence tomography (OCT) showed stage 2 full-thickness macular hole without posterior vitreous detachment (PVD) and operculum formation. Her best-corrected visual acuity (BCVA) was 20/32. One month later, the diameter of the macular hole was getting small and VA improved. Six months later, the macular hole was treated spontaneously with the attached hyaloid membrane to the macula by OCT and the BCVA improved to 20/20. Fourteen months after the first visit, the BCVA decreased to 20/50 and the patient was diagnosed with stage 4 macular hole with complete PVD. OCT showed full-thickness macular hole with a LHEP in the right eye. After 25G-gauge vitrectomy with the peeling of internal limiting membrane (ILM) and LHEP, the macular hole was closed and BCVA finally improved to 20/25. Spontaneous macular hole closure without PVD may rarely occur in patients with LHEP. The surgical removal of ILM and LHEP may contribute to the successful macular hole closure after vitrectomy.

Role of ICAM-1 in impaired retinal circulation in rhegmatogenous retinal detachment.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P < 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (r = - 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r = - 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

Improvement in impaired ocular accommodation by parietal acupoint therapy to relieve neck stiffness: a case report.

OBJECTIVES: Neck stiffness could lead to impaired ocular accommodation. We report two cases that visual function was improved by relieving neck stiffness. CASE PRESENTATION: (Case 1) A 34-year-old female complained of neck stiffness and visual problems after computer work. She was treated by parietal acupoint therapy (PAPT), which is a new scalp micro-acupuncture system. The evaluation of accommodative micro-fluctuations (the Fk-map) showed that increased bilateral ciliary muscle tension in the middle to near distance was relieved bilaterally, accompanied by relief of neck stiffness after treatment. (Case 2) A 43-year-old female complained of a visual problem with pressure pain on the bilateral posterior cervical muscles. Performing with PAPT improved impaired ciliary muscle tension noticeably with relief of neck stiffness after treatment. CONCLUSIONS: This is the first report on the improvement of impaired ocular accommodation with treating neck stiffness by using PAPT.

Evaluation of Chemokine mRNA Expression to Assess Allergic Inflammation of the Ocular Surface in Chronic Allergic Conjunctival Diseases.

PURPOSE: We validated the use of chemokine messenger RNA (mRNA) expression analysis for the assessment of ocular surface allergic inflammation in chronic allergic conjunctival diseases (ACDs) with proliferative lesions, including giant papillae and gelatinous infiltration of the limbus. METHODS: This prospective sectional study included 19 patients with chronic ACDs and 10 healthy volunteers as controls. Patients with chronic ACDs were divided into 2 subgroups according to the severity of the clinical score: active stage ACD subgroup (n = 9) and stable stage ACD subgroup (n = 10). Impression cytology using a filter paper for each upper tarsal conjunctiva of the patients with chronic ACDs and control subjects was performed, and the expression levels of IL1A, CXCL8, IL16, and CCL24 mRNAs encoding interleukin (IL)-1α, CXCL8/IL-8, IL-16, and CCL24/eotaxin-2, respectively, were determined by quantitative real-time polymerase chain reaction using impression cytology specimens. RESULTS: CCL24 and IL16 mRNA levels in the active ACD subgroup were significantly higher than those in the control group (P = 0.003 and 0.004, respectively). IL1A and CXCL8 expression levels in the active ACD subgroup were significantly higher than those in the stable ACD (P = 0.008 and 0.029, respectively) and control (P = 0.008 and 0.014, respectively) subgroups. Furthermore, significant correlations were detected between IL16 and CCL24 mRNA levels (r = 0.76, P = 0.0001) and between IL1A and CXCL8 (r = 0.67, P = 0.0004). CONCLUSIONS: At least 2 kinds of inflammatory reactions, IL-1α- and CXCL8-associated inflammation and CCL24- and IL-16-associated inflammation, may be involved in the exacerbation of chronic ACDs.

[A case of inflammatory granuloma secondary to a foreign body (Cryptomeria) mimicking a bronchial tumor].

This report documents a case of inflammatory granuloma overcoming secondary to a foreign body (Cryptomeria) mimicking a bronchial tumor. A 45-year-old man was referred to the hospital because of hemoptysis and a chronic cough. He had had a chronic cough before visiting the hospital, but had left it untreated for months. A computed tomography (CT) scan showed bronchiectasis in the right lower lobe with evidence of mediastinal lymphadenopathy. Fiberoptic bronchoscopic examinations revealed a tumor with an uneven surface at the orifice of the right B10(b+c), bronchus. The cytological findings of the bronchial tumor showed no malignancy but a predominance of neutrophils. Antibiotics were administered intravenously because of a suspected respiratory infection. After treatment, the abnormal shadows on the chest CT improved. Fiberoptic bronchoscopic examinations showed the bronchial tumor to have disappeared, and a bronchial foreign body was found lodged in the right. B10(b+c) bronchus and it was removed. Pathological examinations and a detailed history revealed that the patient had aspirated a foreign body (Cryptomeria). The tumor was thought to be an inflammatory granuloma secondary to the aspiration of the foreign body. This case highlights the need to search aggressively for foreign bodies in case of clinical symptoms, such as chronic cough, hemoptysis, or findings such as respiratory infection, and bronchial occlusion.

Clinical Usefulness of Simultaneous Measurement of the Tear Levels of CCL17, CCL24, and IL-16 for the Biomarkers of Allergic Conjunctival Disorders.

PURPOSE: This study investigated the clinical usefulness of a multiple tear cytokine/chemokine test by simultaneously determining tear levels of CC chemokine ligand 17 (CCL17)/thymus and activation-regulated chemokine (TARC), CCL24/eotaxin-2, and interleukin-16 (IL-16) for assessing acute and chronic allergic inflammation in allergic conjunctival disorders (ACDs). SUBJECTS AND METHODS: This study included 37 patients with ACD and 11 healthy adults (controls). Patients with ACDs were divided into the following three groups; patients with allergic conjunctivitis (AC group, n = 17), patients with atopic keratoconjunctivitis (AKC group, n = 6), and patients with vernal keratoconjunctivitis (VKC group, n = 14). Tear samples were collected using the Schirmer I method with a filter paper. Tear levels of CCL17/TARC, CCL24/eotaxin-2, and IL-16 were determined by performing a magnetic bead assay (tear cytokine/chemokine test). Tear levels of eosinophil cationic protein (ECP) were determined by performing enzyme immunoassay. In patients with AC, clinical scores of objective findings and results of the tear cytokine/chemokine test at baseline were compared with those at 7 days after treatment with the histamine H1 receptor antagonist (epinastine) ophthalmic solution. RESULTS: Tear positive rates of CCL17/TARC, CCL24/eotaxin-2, and IL-16 were higher in patients with AC, AKC, and VKC compared with controls. Tear levels of CCL17/TARC, CCL24/eotaxin-2, and IL-16 in patients with AKC and VKC were significantly higher than those in patients with AC. Moreover, tear levels of IL-16 in patients with AC that showed improvement of their clinical score by treatment with epinastine ophthalmic solution decreased significantly after 7 days of the treatment compared with those at baseline. In patients with AKC and VKC, a significant correlation was observed between the tear levels of CCL24/eotaxin-2 and ECP. CONCLUSION: Simultaneous measurement of the tear levels of CCL17/TARC, CCL24/eotaxin-2, and IL-16 may be a useful test for assessing acute and chronic allergic inflammation in ACDs.

Efficacy of pneumatic displacement with 40-degree downward gaze positioning for treatment of submacular hemorrhage: report of two cases.

BACKGROUND: Two retrospective case reports are described showing the efficacy of pneumatic displacement with 40-degree downward gaze positioning for treatment of submacular hemorrhage. Case 1 involved an 85-year-old woman who visited our clinic with a complaint of blurred vision in her right eye. Best corrected visual acuity (BCVA) of the right eye was hand motion. Her right eye showed a submacular hemorrhage with retinal macroaneurysm. Prone positioning was difficult because of the patient's age and obesity. The treatment method was pneumatic displacement with 40-degree downward gaze positioning after intravitreal injection of 100% sulfur hexafluoride gas. After the treatment, the hemorrhage moved downward and BCVA of her right eye was 0.1. Case 2 involved a 58-year-old man with a complaint of blurred vision in his left eye. BCVA of his left eye was 0.3 and submacular hemorrhage was observed. He underwent displacement of the hemorrhage as previously described. After treatment, the submacular hemorrhage moved downward. Angiography detected a polypoidal lesion with a vascular network. upon diagnosis of polypoidal choroidal vasculopathy, bevacizumab was injected intravitreally. Two months after gas injection, the submacular hemorrhage disappeared. Optical coherence tomography showed flattening of the submacular retinal pigment epithelium, which was not observed prior to bevacizumab therapy. BCVA of the patient's left eye was 0.9. Pneumatic displacement with 40-degree downward gaze positioning after intravitreal sulfur hexafluoride injection is useful to displace a submacular hemorrhage. Early application of this treatment provides improvement of vision and facilitates fundus examination, which could reveal the cause of the submacular hemorrhage.