気管支分岐異常とCOPD発症の関連性

気管支の分岐を規定する変異は26％に存在

• 最も多い気管支分岐変異(sub-superior *の存在)は、COPD、慢性気管支炎オッズ比増加と関連し、中枢側気道の分岐数増加や、全肺葉の気腔拡大、気腫と関連。
• 2番目に多い変異（右B7の欠損）は、喫煙者COPDオッズ増加、呼吸困難、全ての肺葉の小気道内腔狭窄化と関連し、FGF10遺伝子多様性 と関連

Human airway branch variation and chronic obstructive pulmonary disease
Benjamin M. Smith, et al. and for the MESA Lung and SPIROMICS investigators
PNAS 2018; published ahead of print January 16, 2018, https://doi.org/10.1073/pnas.1715564115



in vivo central airway branch variant(s)

気道３D再構成
A) 標準下葉解剖：両側　下葉上区(B6)、前区(B8)、外側区(B9)、後区域(B10)の存在と、右B7の存在と、左B7の欠損、B※の欠損

B) 副上枝下下葉分岐変異:accessory subsuperior airway branch variant

(sub-superior *もしくはsub-superior BX*9 or BX*10は、本来は、背側、B6とB9を起始として、左葉 29％、右葉 62%に存在)

C) 右内側肺底部分岐欠損:absent right medial-basal airway branch variant

(B7気管支は通常B7a、B7ｂに分岐し、14-18%で存在しない）

 大きな気道の形態的変化が、COPDや症状とに関連性があることは、臓器形成期、既に、その後の疾患進行に関連するリスクを伴っていることを表す。画像診断でその後のリスクが明確になれば集約的な介入も可能となるのかもしれない。

上腹部手術：術前理学療法１回で術後呼吸器合併症半減

単回術前の理学療法は上腹部手術後術後呼吸器合併症： postoperative pulmonary complications (PPCs)減少効果


上腹部手術後の呼吸器系合併症の発生頻度は10〜50%で、死亡率とも関連。術前に患者教育、トレーニングの機会を与えることで、PPC頻度減少できるか？


Lung Infection Prevention Post Surgery Major Abdominal with Pre-Operative Physiotherapy (LIPPSMAck-POP) による仮説：術前教育、呼吸運動訓練によるPPCs抑制効果



Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial

Ianthe Boden,  et al.
BMJ 2018; 360 doi: https://doi.org/10.1136/bmj.j5916 (Published 24 January 2018)
Cite this as: BMJ 2018;360:j5916

18歳以上待機的上腹部手術予定6週間以内441名
情報冊子(n=219; 対照) vs 術前理学療法(n=222;介入群)
12ヶ月フォローアップ


情報冊子(対照)
付加的な30分理学療法教育と呼吸運動トレーニングセッション（介入群）

教育はPPCの存在と、術後意識回復直後から開始すべき早期歩行と自己訓練呼吸運動

主要アウトカムは、術後14入院日内のPPC評価、Melbourneグループスコア


Box 1 Postoperative pulmonary complication diagnostic tool: Melbourne group score
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Diagnosis confirmed when four or more criteria are present in a postoperative day:

• New abnormal breath sounds on auscultation different from in the preoperative assessment
• Production of yellow or green sputum different from in the preoperative assessment
• Pulse oximetry oxygen saturation (SpO2) <90 air="" consecutive="" day="" li="" more="" on="" one="" postoperative="" room="" than="">
• Maximum oral temperature >38°C on more than one consecutive postoperative day
• Chest radiography report of collapse or consolidation
• An unexplained white cell count greater than 11×109/L
• Presence of infection on sputum culture report
• Physician’s diagnosis of pneumonia, lower or upper respiratory tract infection, an undefined chest infection, or prescription of an antibiotic for a respiratory infection

・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・

セカンダリアウトカムは、院内肺炎、入院日数、CU利用、入院コスト
患者には健康関連QOL,肺機能、他院後合併症を6週間後測定、全原因死亡率は12ヶ月測定


結果
術後入院14日以内のPPC発生頻度は、院内発症肺炎含め、介入群においては対照群の半減　 (補正ハザード比 0.48, 95% 信頼区間 0.30 to 0.75, P=0.001)、絶対リスク減少として15% (95% 信頼区間 7% to 22%)、NNT17（95％信頼区間 5-14)
他のセカンダリアウトカムにおいては有意差認めず

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悪性胸膜中皮腫治療：ASCO臨床実践ガイドライン

Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline
Hedy L. Kindler, et al.
http://ascopubs.org/doi/full/10.1200/JCO.2017.76.6394


Recommendation 2.1: The recommended first-line chemotherapy for patients with mesothelioma is pemetrexed plus platinum. However, patients should also be offered the option of enrolling in a clinical trial (Type of recommendation: evidence based; Evidence quality: high; Strength of recommendation: strong)

アリムタ：ペメトレキセド＋プラチナ製剤を第一選択とする

Recommendation 3.1: The addition of bevacizumab to pemetrexed-based chemotherapy improves survival in select patients and therefore may be offered to patients with no contraindications to bevacizumab. The randomized clinical trial demonstrating benefit with bevacizumab used cisplatin/pemetrexed; data with carboplatin/pemetrexed plus bevacizumab are insufficient for a clear recommendation (Type of recommendation: evidence based; Evidence quality: high; Strength of recommendation: moderate)

ペメトレキセド・ベースの化学療法に、アバスチン：ベバシズマブ（Bevacizumab）を追加は選択的患者で禁忌のない場合、投与可


Recommendation 3.2: Bevacizumab is not recommended for patients with PS 2, substantial cardiovascular comorbidity, uncontrolled hypertension, age > 75, bleeding or clotting risk, or other contraindications to bevacizumab (Type of recommendation: evidence based; Evidence quality: intermediate; Strength of recommendation: moderate).
ベバシズマブはPS2、心血管併発、高血圧コントロール不良、75歳超、出血・血栓リスク、禁忌では推奨しない

Recommendation 4.0: In patients who may not be able to tolerate cisplatin, carboplatin may be offered as a substitute for cisplatin (Type of recommendation: evidence based; Evidence quality: intermediate; Strength of recommendation: strong).
シスプラチン、カルボプラチン耐用不能患者では、シスプラチンを除いて投与

Recommendation 5.1: Retreatment with pemetrexed-based chemotherapy may be offered in pleural mesothelioma patients who achieved durable (> 6 months) disease control with first-line pemetrexed-based chemotherapy (Type of recommendation: evidence based; Evidence quality: low; Strength of recommendation: moderate).
ペメトレキセド基本の再治療は、1stラインのペメトレキセド化学療法にてコントロールの６ヶ月超耐用可能な胸膜中皮腫患者で投与可能

Recommendation 5.2: Given the very limited activity of second-line chemotherapy in patients with mesothelioma, participation in clinical trials is recommended (Type of recommendation: evidence based; Evidence quality: intermediate; Strength of recommendation: strong).


Recommendation 5.3: In patients for whom clinical trials are not an option, vinorelbine may be offered as second-line therapy (Type of recommendation: evidence based; Evidence quality: low; Strength of recommendation: moderate).

Recommendation 6.1: In asymptomatic patients with epithelial mesothelioma and a low disease burden who are not surgical candidates, a trial of expectant observation may be offered before initiation of systemic therapy (Type of recommendation: evidence based; Evidence quality: low; Strength of recommendation: moderate).

Recommendation 6.2: Front-line pemetrexed-based chemotherapy should be given for four to six cycles. For patients with stable or responding disease, a break from chemotherapy is recommended at that point (Type of recommendation: evidence based; Evidence quality: low; Strength of recommendation: moderate).