Therapeutic effect of nintedanib on acute exacerbation of interstitial lung diseases.

Although the development of new antifibrotic agents (pirfenidone, nintedanib) has modified the disease progression of idiopathic pulmonary fibrosis (IPF), there is still no effective treatment for acute exacerbation of interstitial lung diseases (ILD) including IPF. We herein report a case of acute exacerbation of ILD (AE-ILD) treated only with nintedanib without any environmental changes and any other medications such as corticosteroid therapy, diuretic and anti-biotics, which resulted in the gradual improvement of the patient's clinical symptoms, high-resolution computed tomography findings, and forced vital capacity. This case might suggest the possibility that nintedanib not only modifies the disease progression of Idiopathic Pulmonary Fibrosis (IPF), but also facilitate the recovery from the acute exacerbation of ILD.

Remission of ALK-negative primary pulmonary inflammatory myofibroblastic tumor on treatment with clarithromycin: A case report and review of the literature.

Inflammatory myofibroblastic tumors (IMTs) belong to an intermediate group of soft-tissue tumors, they are relatively rare but exhibit a wide range of pathologies, from benign to malignant. At present, no standard treatment has been established, however, it is known to be important to determine the grade of malignancy of the tumor, prior to treatment. The present study reports a 73-year-old female patient with no clinical manifestations, who, when examined radiographically at a health check exhibited bilateral thoracic infiltrative shadows and nodular shadows by chest CT. A metastatic tumor or an organizing pneumonia were suspected. Blood examination showed no abnormal findings, and a pathological diagnosis of IMT was given from the histological findings of the tissue extracted by video-assisted thoracic surgery. Histological analysis established the lack of expression of anaplastic lymphoma kinase (ALK1) and immunoglobulin subtype G4 (IgG4). Alteration of the radiological shadows was observed over several weeks, and after concluding that chronic inflammation was worsening the patient's condition, clarithromycin was administered as a long-term macrolide therapy. The IMT decreased in size, and eight months later it had almost resolved. The patient was last reported to be maintaining a stable condition with no relapse. Some IMT cases have malignant pathology, and should be carefully followed-up. However, in the present case, where the IMT is both ALK1-negative and IgG4-negative, its biological immune responsiveness appears to differ from positive cases, and an inflammatory response was predominant. Clarithromycin, has immunomodulatory and anti-inflammatory effects and appeared to be effective in treating the IMT of the patient in the present study.

Clinical factors associated with negative urinary antigen tests implemented for the diagnosis of community-acquired pneumococcal pneumonia in adult patients.

OBJECTIVE: This study investigated clinical factors associated with negative urinary antigen tests (UAT) implemented for the diagnosis of pneumococcal community-acquired pneumonia (CAP) in adult patients. SUBJECTS AND METHODS: We reviewed the medical records of 755 adult patients who completed the UAT in our hospital between 2009 and 2012. Of these, we evaluated 63 patients with bacteriologically confirmed definite pneumococcal CAP (33 were UAT-positive, and 30 were UAT-negative). RESULTS: There was no significant difference between the UAT-positive and the UAT-negative patients regarding age, dehydration, respiratory failure, orientation, blood pressure (ADROP) score (the CAP severity score proposed by the Japanese Respiratory Society), gender, white blood cell counts, liver/kidney function tests, or urinalysis. However, serum C-reactive protein (CRP) concentrations were 31% lower in the UAT-negative patients than in the UAT-positive patients (p = 0.02). Furthermore, the prothrombin time-international normalized ratio was 50% higher in the UAT-negative patients than in the UAT-positive patients, although the difference did not reach statistical significance (p = 0.06). The prevalence of comorbidities was similar in both UAT-positive and UAT-negative patients. However, warfarin had been prescribed in 8 (27%) of the UAT-negative patients compared to only 1 (3%) of the UAT-positive patients (odds ratio = 11.6; p = 0.01). CONCLUSIONS: These results suggested that low serum CRP concentrations and the use of warfarin increased the possibility with which false-negative UAT results occurred in these patients with pneumococcal CAP.

Tracheobronchial foreign body aspiration demonstrating serial bronchopulmonary changes on computed tomography.

INTRODUCTION: Tracheobronchial foreign body may often be treated as asthma, chronic bronchitis or etc. especially in patients with no memories of aspiration episodes. CASE PRESENTATION: A 74-year-old woman, suffering from persistent cough, was temporarily misdiagnosed with allergic bronchopulmonary aspergillosis and treated for six months. During this period, computed tomography (CT) findings changed from thickened bronchial walls and a "tree-in-bud" pattern to clubbing bronchiectasis and atelectasis, and no significant bacteria was detected. Finally, a vegetable core was subsequently extracted via flexible bronchofiberscopy. Although the patient's symptoms improved dramatically, the bronchopulmonary lesion remained practically. CONCLUSIONS: We assume that chronologic CT findings of the bronchopulmonary damage by aspiration of a vegetable core, without significant detection of bacteria during the course, will be quite valuable for clinicians.

Lung metastasis of transitional cell cancer of the urothelium, with fungus ball-like shadows closely resembling aspergilloma: A case report and review of the literature.

The present study reports the case of a 67-year-old female patient who was initially diagnosed with pulmonary aspergilloma. This diagnosis was based on a chest computed tomography (CT) scan showing a cavitary lesion of 3.5 cm in diameter, with fungus ball-like shadows inside, and an air crescent sign in the right upper lung. At 63 years old, the patient was treated for transitional cell cancer of the urothelium (non-invasive, pT1N0M0) by total cystectomy, ileal conduit diversion and urostomy. For 4 years post-operatively, the patient was healthy and had no clinical symptoms, and the air crescent sign was not identified by chest CT until the patient had reached 67 years of age. However, a final diagnosis of lung metastasis of transitional cell cancer of the urothelium was histopathologically identified subsequent to video-assisted thoracic surgery. Although it is rare that transitional cell cancer moves to the lung and makes a cavitary lesion, a differential diagnosis of cancer is necessary, even when examining infected patients with air crescent signs that are characteristic of aspergilloma. The physician must be mindful of metastatic pulmonary tumors that closely resemble aspergillomas, not only in infectious diseases, but also in oncological practice. Primary surgical removal should be considered.

Palliation of malignant tracheal stenosis with a second implantation of an expandable metallic stent under endotracheal intubation.

A 74-year-old man was admitted with respiratory failure and treated for tracheobronchial stenosis due to metastasis of renal cell carcinoma. It improved after implantation of an expandable metallic stent (EMS). One year later, the metastatic tumor at the near distal side of the EMS increased; eventually serious respiratory failure occurred again. However, the delivery catheter of EMS could not be inserted by the usual procedure because there was a strong tracheobronchial curve. Finally it passed along the inside of the endotracheal intubation tube. The respiratory failure was improved by the second implantation of EMS with the method of stent in stent. EMS is often effective in a case with a strong curve and twist of the trachea/bronchi. It was also considered one way of letting the delivery catheter pass inside the endotracheal intubation tube if the patient's respiratory condition was maintained.

Bronchial asthma developing after 15 years of immunosuppressive treatment following renal transplantation.

A 42-year-old woman who underwent renal transplantation from her mother at the age of 26 due to IgA nephropathy had since been treated with immunosuppressive agents, including prednisolone (PSL), azathioprine (AZA) and cyclosporine (CsA). The patient had remained clinically stable for 15 years. However, in the middle of May 2010, she developed bronchial asthma for the first time after performing house-cleaning activities and was treated with corticosteroids and antiasthmatic agents. The use of immunosuppressive agents as a treatment for severe bronchial asthma might have been related to the manifestation of bronchial asthma in this case.

[Flow and inspiratory pressure characteristics of In-Check(tm) and training whistles].

BACKGROUND: The optimal inhalation effort using dry powder inhalers (DPI's) varies with the specific inhaler. Accordingly, the device used for instruction in the proper use of the specific DPI should have physical characteristics similar to the actual DPI. However, the precision with which these devices mimic the actual DPI's has not been established. METHODS: We measured mouthpiece pressure (PI) and flow through the In-Check with an added flow resistance (for DiskusTM, DiskhalerTM, PulmicortTM, HandihalerTM, and ClickhalerTM) and the training whistles (for Diskus, Pulmicort, SymbicortTM, TwisthalerTM) at different inhalation pressures. RESULTS: Both the In-Check with an added flow resistance for individual DPI and the training whistles for each DPI had parabolic PI-flow relationships similar to the actual DPI. When a curve was drawn from direct readings of the In-Check scale, it fell consistently below that based on the pneumotachometer values. PI-flow curves of the actual DPI fell below both of the above curves. Among the same type of DPI, PI-flow relationships resembled each other, but one of 13 in the Diskus group demonstrated curves above and one of 6 in Pulmicort demonstrated curves below the others. The flows at which sounds were generated from the whistle were between 25-50 L/min. CONCLUSIONS: Both In-Check and training whistles had suitable PI-flow relationships. Flow readings taken directly from In-Check tended to be lower than the measured value. A few training whistles might generate sounds with efforts below the optimal one.

[The relationship between inspiratory pressure and flow through dry powder inhaler available in Japan].

OBJECTIVE: Recently many of the inhaled drugs are provided as dry powder formula and prescribed for such diseases as COPD and asthma exacerbation. Inspiratory flow rate through the dry powder device (DPI) has a significant influence on therapeutic response in these disease conditions. We planned to measure flow vs. pressure relationships of almost all of the DPIs available in Japan. METHODS: Driving pressure (PI) and flow through the DPI were measured and the linear regression lines between PI and flow(2) were drawn. RESULTS: The slope and intercept of the regression lines were as follows: Turbuhaler for Pulmicort 79.26 (l/s)(2)/cmH2O, 626 (l/s)(2), Turbuhaler for Symbicort 88.99, 688, Twisthaler 56.37, 478, Diskus 125.98, 872, Diskhaler, 166.98, 780, Handihaler, 54.88, 498, Clickhaler, 78.37, 452. We drew P(I) vs flow curves of each DPIs for instruction of DPI devices to the patients. CONCLUSION: Inspiratory pressure is an excellent parameter to indicate optimal flow through DPI. Early escalation of medication may be important in the patients using Turbuhaler or Twisthaler that has higher resistance in inspiratory channel.

The efficacy of an oxygen mask with reservoir bag in patients with respiratory failure.

BACKGROUND: Oxygen masks with reservoir bags (OMR) are widely used for oxygen therapy in patients with severe respiratory failure. The purpose of the present study was to determine whether OMRs are effectively used in clinical practice. METHODS AND RESULTS: In the first phase of the study on the patients with severe respiratory failure, no apparent respiratory motions of the reservoir bag were noted, and the oxygen saturation level as determined by pulseoximetry (SpO2) did not decrease even after shrinkage of the reservoir bag. In the second phase, when a healthy female volunteer wore an OMR, pressure swings in the reservoir bag were less than 0.1 cmH2O, even when she was breathing with her maximal respiratory efforts (tidal volume, 1.14 L and respiratory frequency, 19.2 bpm). These pressure swings provoke a less than 50 mL oxygen supply from the reservoir bag. The decreased efficacy of OMR in oxygen therapy may be primarily due to the large space between the OMR and the nose but this space is inevitable in sitting or orthopneic subjects. CONCLUSIONS: Fixing an OMR very tightly to the face is mandatory for its effective use. It should also be kept in mind that there are limitations to the efficacy of OMR, even when they are used with such careful management.

Aerosolized methacholine-induced bronchoconstriction and pulmonary hyperinflation in rats.

The body plethysmography (BPG) is a useful tool for analyzing pulmonary function in small animals because it simultaneously measures airway resistance (R (aw)) and functional residual capacity (FRC). We previously described a BPG with the enclosed environment maintained at body temperature and water vapor-saturated. We found dose-dependent increases in R (aw) in response to inhaled methacholine (Mch) with no apparent increase in FRC in intratracheally intubated rats without paralysis. To resolve this apparent inconsistency in clinical observations, we repeated the study using a newly developed BPG that allowed us to shorten the interval between Mch-inhalation and measurements by about two-thirds. Using Mch concentrations of 0, 0.5, 1.0, 2.0 and 4.0 mg/ml each for 2 min, both parameters increased in a dose-dependent fashion with FRC (mean +/- SE) values of 3.77 +/- 0.16, 4.43 +/- 0.26, 4.75 +/- 0.34, 5.02 +/- 0.49 and 5.34 +/- 0.38 ml and R (aw) values of 18.6 +/- 3.9, 21.6 +/- 4.9, 35.0 +/- 6.9, 49.0 +/- 8.8 and 65.7 +/- 8.8 ml/s/Pa, respectively. Immediate measurement after Mch-inhalation demonstrated profound bronchoconstriction associated with dose-dependent increases in FRC.

[A case of severe bronchial stenosis caused by a vascular ring in an elderly woman].

We report a case of bilateral severe bronchial stenosis which was caused by compression by ascending and descending portions of the aorta. Asthma-like symptoms developed 9 years previously and dilation of the ascending aorta was noted 2 years previously. Bronchial obstruction was suspected because of diminishing breath sounds in the left hemithorax. Investigations suggested existence of a vascular ring consisting of the left aortic arch, right descending aorta and possibly the right ligamentum arteriosum. The patient fell in shock during bronchoscopy. Emergency implantations of bronchial stents in the right bronchus and then the left bronchus were made. Because of the patient's poor lung function, there was an extremely high risk for surgical treatment. Although airway stenosis caused by vascular anomaly in elderly patients is very rare, when asthma-like symptoms developed in patients with a right-sided descending aorta, physicians should consider the possibility of such condition.

[Exacerbation of obstructive sleep apnea syndrome at altitude 3,850 m].

Recently more people visit extremely high-altitude places for sightseeing or business. As a result, patients with obstructive sleep apnea (OSAS) also are likely to stay at such places. However the changes of severity of OSAS at extremely high-altitude are not certain. A 44-year-old man was given a diagnosis of OSAS in 2004 and had been using continuous positive airway pressure CPAP at night. On a visit to Nepal the severity of his OSAS was evaluated at Kyanjing Gompa (3,850 m) and at other places. At Kyanjing Gompa, his apnea-hypopnea index (AHI) was 41.8/hr on one night and 52.2/hr on another night, and the periods of SpO2 less than 85% were 51.4% of total sleeping duration and 83.2% respectively. When he returned to Hachioji (altitude 150 m), his AHIs were 10.5/hr and 9.5/hr on two consecutive nights. These results suggested that OSAS worsened by persistent hypobaric hypocapnia and by developing periodic breathing.

A case of pulmonary semi-invasive aspergillosis developing fatal acute exacerbation.

A 80-year-old male was referred for detailed examination of left apical fibrotic changes in the chest radiograph. Six years later, several cavitary lesions with thickening of the pleura developed. Anti tuberculosis therapy had no effects. Despite intravenous administration of antibiotics, the cavities became larger and the infiltrates progressed to the left lower lobe. The air crescent was observed in one of the cavities. Repeated sputum examinations revealed Aspergillus niger only. With administration of anti fungal drug, infiltrates were faded. Four months after the cessation of antifungal drug high fever associated with new infiltrates developed. Sputum culture showed Aspergillus flavus. Infiltrates over the entire left lung field and in the right upper lobe were observed. On CT film necrotic lung tissue was strongly suggested in the cavity. The patients died of respiratory failure. Although initial course of the presented case was compatible with semi-invasive pulmonary aspergillosis (SIPA), fluminant and fatal exacerbations which may be very unusual in SIPA, developed in later. The mycetoma-like ball may be occasionally made of necrotic lung parenchyma instead of fungal mycelia in SIPA.

Functional residual capacity and airway resistance in rats of COPD model induced by systemic hyaluronidase.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is characterized by obstructive bronchiolitis and parenchymal destruction. In animal models, air space enlargement induced by intratracheal elastase is augmented by prior depletion of lung hyaluronan by hyaluronisase. Recently our colleagues reported that intravenous hyaluronisaein in the absence of elastase produced emphysema-like alveolar dilation [1]. In this study we measured functional residual capacity (FRC) and airway resistance (Raw) in the rats with hyaluronidaseinduced experimental COPD. MATERIALS AND METHODS: Hyaruonidase (20 mg/kg) was administered from the caudal vein of 19 male Wistar rats (COPD rats). Two weeks after the injection, FRC and Raw were measured with bodyplethysmogarph. RESULTS: Thickness or inflammatory cell infiltrations were not apparent in the bronchus of the COPD rat while alveolar distension was obvious. The mean FRC of the COPD rats (6.22 ± 1.00 ml, mean ± SD) was significantly larger than that of Control rats (5.48 ± 0.85 ml). There was no statistical significance between the mean Raw of the COPD rats (0.28 ± 0.08 cmH2O/ml/s) and that of the control rats (0.28 ± 0.13 cmH2O/ml/s). CONCLUSION: Systemic administration of hyaluronidase produced pulmonary overinflation but did not bronchial constriction. We speculate that hyaluonidase-induced COPD simulates panlobular emphysema.

Parasympathetic neural control of canine tracheal smooth muscle.

The middle segment of the trachea is innervated by the recurrent laryngeal and pararecurrent nerves. This study determined the pathway that mediated descending commands to the tracheal smooth muscle. Animals used were seven paralyzed and tracheostomized dogs. Tracheal contraction induced either by apnea, mechanical stimulation of the tracheal bifurcation or hypercapnia was always composed of tonic and rhythmic components. The rhythmic contraction developed in synchrony with rhythmic bursts on phrenic nerve activity (PNA). The respiratory-related bursts were also observed on the recurrent laryngeal nerve activity (RNA) and pararecurrent nerve activity (ParaRNA). During apnea there was no tonic activity neither on RNA or PNA, whereas ParaRNA had both tonic and rhythmic activities. Bursts on RNA preceded to correspondent PNA-bursts by 90+/-13 ms. In contrast, ParaRNA-burst always developed later than PNA-burst and it started at almost the same time as that of tracheal rhythmic contraction. During mechanical stimulation of the trachea or CO2-loading, though RNA did not include tonic component, ParaRNA had tonic activity during tracheal tonic contraction. These findings suggested that rhythmic and tonic contractions of the trachea were mediated through the pararecurrent nerve but not through the recurrent laryngeal nerve.

A case of the diaphragmatic flutter with an electromyographic study of the respiratory muscles.

A 28-year-old female was complained with dyspnea and involuntary rhythmic movements in her chest and upper abdomen. Diagnosis of the diaphragmatic flutter was established since high frequency intermittent discharges of the respiratory muscles superimposed on her ordinary respiratory activities. The origin of these abnormal discharges may be in the central nervous system and the psychosomatic factor is participating in the development of the diaphragmatic flutter.

Effect of the respiratory-related bronchial rhythmic constriction on alveolar ventilation in the dog.

The middle-sized bronchus constricts during mid-inspiration through early-expiration. The purpose of this study was to elucidate the physiological role of this respiratory-related bronchial rhythmic constriction (RRBRC). The following parameters were measured in 12 decerebrated and paralyzed dogs: pressure from a balloon-tipped catheter in the fifth-generation bronchus (to reveal RRBRC), efferent neurogram from C(5) phrenic, and ventilatory flow and volume. We found a small but significant reduction of peak expiratory flow of mechanical ventilation during RRBRC. During bilateral vagal cold block, RRBRC was simulated by intermittent electric stimulation of vagal fibers distal to the cold block. This stimulus evoked a decrease in peak expiratory flow and in Pa(CO2) (approximately 1.5 mmHg). After vagal warming, mechanical ventilation was terminated, and blood gases were maintained normal by extracorporeal oxygenation. During each RRBRC ventilatory volume decreased by approximately 3 ml. The changes in gas volume and RRBRC disappeared after bilateral vagotomy. These findings support the concept that the physiological role of RRBRC is to facilitate alveolar gas exchange by reducing expiratory flow, anatomical dead space, or both.

Effects of bronchial intermittent constrictions on explosive flow during coughing in the dogs.

This study tested the hypothesis that intrathoracic bronchi intermittently constrict during coughing and attempted to elucidate the effect on explosive flow. The subjects were 21 dogs having undergone tracheostomy. In the first group A (n = 7), the diameter of the fifth-generation bronchus was measured with a balloon-tipped catheter and the change during coughing was analyzed. In the other group (n = 14), the dogs were vagotomized and coughing was simulated by sequential application of positive and negative airway pressures (sham cough). The effects of the bronchial constriction, elicited by the stimulation of vagus efferent fibers, on explosive flow and airway pressure of sham cough were analyzed. The bronchus was constricted in explosive phase of spontaneous coughing in all the dogs of the first group. When cough bouts were repetitively developed, bronchial constriction and phrenic burst developed simultaneously. The intermittent bronchial constrictions fused and virtually acted as tonic constriction. In the second group of dogs the explosive flow of sham cough consisted of two phases; a short bout followed by a near-constant flow. When the bronchus was constricted, the explosive flow was still biphasic in 12 dogs and an exponential decay pattern formed in 2 of them. In these 12 dogs, the peak explosive flow slightly but significantly decreased (mean +/- SD, 1.39 +/- 0.23 vs. 1.34 +/- 0.23 l/s) and airway pressure in the segmental bronchus became smaller (-1.18 +/- 0.53 vs. -0.15 +/- 0.94 cmH(2)O). We concluded that intermittent bronchial constrictions act as tonic one during coughing. Bronchial constriction slightly decreased the peak explosive flow and moved the choke point to the proximal airway.

Impact of Fluticasone Diskhaler on health-related quality of life in asthmatic patients.

OBJECTIVE: To assess effect of a breath-actuated inhaled steroid, Fluticasone Diskhaler (Flutide) on health-related quality of life in asthmatic patients using Hyland's living with asthma questionnaire (LWAQ). SUBJECTS AND METHODS: Randomly selected asthmatic patients filled out the LWAQ (the first study). Then, the eight physicians switched inhaled steroid from pressurelized metered-dose inhaler of beclomethasone (BDI) to Flutide according to their own decision. Consequently some patients were switched their prescriptions and others were not. In 12 weeks after the first study, all the patients again filled out the LWAQ (the second study). RESULTS: The patients treated with Flutide were 87 and without were 159. The scale scores of the Flutide group (mean, 1.900) were significantly higher than those of the BDI-group (mean, 1.789). In the second study, there was no significant difference between the scale scores in the two groups (mean, 1.782 vs. 1.705). Among the 8 domains, only medication score significantly decreased by Flutide therapy. More than 80% of the patients favored easy handling of Flutide including no necessity of the spacer. CONCLUSIONS: Flutide therapy significantly improved quality of life in asthmatic patients. The possible mechanisms are the stronger effectiveness of fluticasone propionate and improvement of adherence to inhaled steroid.