喘鳴、喘息とマルファン症候群との関係は？

How are wheezing and asthma connected to Marfan syndrome?

Interestingly, we see a great deal of wheezing in both children and adults with Marfan syndrome and it's somewhat of a complex kind of symptom in Marfan syndrome because the cause of the wheezing can be very different than wheezing in the general population.

興味深いことですが、マルファン症候群の成人、小児でかなりの喘鳴が認められます。マルファン症候群の場合は、一般人の喘鳴とは原因が大きく異なることがあるため、症状は多少複雑になります。

One issue is, as I was telling you before, that some of the chest wall abnormalities that we see can cause abnormal development of the lungs. They can also cause abnormal development of the airways and the airways are tubes that conduct oxygen into the alveoli where oxygen goes into the blood.

一つの問題としては、以前お話したように、胸壁の異常は肺の形成不全を招くことがあるということです。また、胸壁異常により、気道形成にも問題が生じることがあります。気道とは管のことですが、その中を通って酸素が肺胞へ移動し血流へと入ります。

And so what happens is that these tubes can actually get very narrowed because of where they're positioned in the chest and when they become narrow, they're susceptible to kind of what we call wheezing because there's airway obstruction and so that's a cause of airway obstruction. That's not a classic cause that you would see in someone who doesn't have Marfan's syndrome because that's a result of a restrictive process and not what we would call a reactive process or an allergic process which is what we see kind of in most people who don't have Marfan syndrome.

胸腔内での位置関係から、気道は非常に狭くなることがあり、気道の閉塞により喘鳴が生じやすくなりますが、これは一般人でみられる喘鳴の原因とは異なっています。というのは、一般人の喘鳴の原因は反応性あるいはアレルギーによるものだからです。

The other issue is that, and this is something that's kind of emerging from some of the resources going on in Marfan syndrome and Loeys-Dietz syndrome, is there seems to be some primary defect in the inflammatory cells that lead to an asthma or an allergic phenotype in patients with Marfan syndrome and so it may be that those disturbances underlie a primary predisposition to develop asthma and that's one of the areas of research that we're investigating at Hopkins.

他の問題としてはマルファン患者では、炎症細胞において根本的な異常がいくつか生じており、これにより喘息あるいはアレルギー表現型が発症するというものです。これはマルファン症候群あるいはロイス・ディーツ症候群の進行中の研究から得られたものです。この異常が喘息発症の主な素因となっている可能性がありますが、これについては現在ジョンズ・ホプキンス大学で研究が進行しています。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。

6分間歩行テストについて

What is a "6 minute walk test" and why is it helpful for people with Marfan syndrome?

One study that and I think more and more of the Mafan patients that I consult on are having is what I call an exercise study, which is a quantitative measurement of exercise capacity because my feeling is that whenever you come into the medical system and you say you have a symptom. What we need to do is somehow qualify it, quantify it and then what we can do is determine whether our interventions have actually been effective and you have a number in your head to say, "Okay, I'm starting here." "I would want to maintain this," "I don't want to get worse," or "I want to get better."

私が担当する多くのマルファン患者を対象に行われている研究は、運動研究と呼ばれています。この研究は運動能力を定量的に測定することを目的としています。これを行う理由は、患者さんが訴えた症状を何らかの方法で特定し、定量化することが必要になるからです。我々は手術が実際に効果があったかどうかを確認するわけですが、検査では、患者さんに数字を思い浮かべてもらい、「スタートはこの数字にします」「この数字を維持できるようにしたい」「これ以上苦しいのはダメ」「もっと楽にできるようになりたい」など検査についてのコメントをもらいます。

And the study that best does that, that isn't terrifically kind of involved, and isn't so hard to arrange is what I call a six-minute walk test and it's a test we performed very commonly in a variety of chronic lung disorders and it's very suitable for Marfan patients because it can tell us what the actual limitations in their exercise capacity is, relative
to other people of the same age, the same gender and it's very, very easy to perform.

こういったやり取りが可能で、それほど負荷がかからず、準備に手間どらない検査が、「6分間歩行テスト」なのです。様々な慢性肺疾患の検査でごく普通に行っているもので、マルファン患者さんにも、うってつけです。その理由は同年代や同性の人と比べた運動能力の限界がわかるからです。それにとても簡単にできます。

And so I tell many patients to ask their physicians to order a six-minute walk test and even if their interpretation is not so refined, they can always send the test results to me or to people like me to have us kind of weight in, help their physicians at home understand what they're looking at and often they'll have six minute walk tests that are much better than they had anticipated and that's really encouraging because then it says, "Okay I'm actually not doing badly, but what can I do to maintain this level of functioning? And what can I do to potentially improve it?" and it just gives you a place to be and I think that is always so useful as you're thinking about interventions going forward.

ですから私は多くの患者さんに、主治医に「6分間歩行テスト」をしてもらえるようお願いしてくださいとお話しています。主治医の先生が出した結果が正確でないとしても、私や私のような専門家に結果を送付していただければ、理解のお手伝いができます。多くの場合、「6分間歩行テスト」の結果は想像以上のメリットをもたらしますし、患者さんの励みにもなります。「悪くなってはいないようだけど、今の状態を維持するにはどうしたらいいのかな？どうしたらもっといい結果になるだろう？」といった具合です。自分の状態を客観的に判断できますし、手術を考えている際には毎回非常に役立ちます。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。

拘束性肺疾患に適した治療は？

What is the appropriate treatment for restrictive lung disease?

One of the aspects of restrictive lung disease that I encourage patients to really think about and discuss with their physicians is whether the surgical intervention that are being proposed will actually either maintain their level of lung function or improve it because unfortunately, I think it's because there are so many different surgeries that are offered to patients with Marfan syndrome and they have to be responsible for understanding the literature and the history, the expectations for every one of these surgical interventions.

肺が狭められることで発症した疾患に関し、よく考えて主治医と相談するようにお勧めしていることは、提案された手術によって本当に肺機能が維持されたり、回復するのかを確認するということです。理由は、マルファン患者さんに提案される手術は多種多様であり、文献や既往、手術の予後などを理解することが求められるからです。

And for interventions in the chest, there's a component of what we call cosmesis; that's appearance and there's also a component of what we call function and those can be very much separated and divided.

胸部への介入については、外見に関わる美容という側面があり、その他に機能という側面もあります。これらは大きくかけ離れたものです。

For example, pectus excavatum is a very common, just deformity in Marfan syndrome and it's typically kind of manifest and many people have it who don't have Marfan syndrome; it's the most common chest wall disorder in the general population and what it is is a depression of the sternum or the central part of your chest.

例えば、漏斗胸はマルファン症候群では非常に一般的な胸部の奇形で目立つものですが、多くの健常者にも見られます。一般人に最も多い胸壁異常であり、胸の中央が陥没する所見です。

And for some people and for some kids especially who have this, it's a major source of discomfort, especially around other kids who may see it when they're in gym class, when they go swimming and what I encourage parents to do is to take that discomfort seriously and if there's an intervention plan, simply because you have a child who feels uncomfortable and finds this kind of a socially kind of disturbing situation, that's a reason to intervene.Unfortunately, that rationale for a surgical procedure gets very much tied into, "Will this improve my child's lung function?"

この所見をもつ成人の一部や特に一部の子供では、精神的苦痛の大きな理由となっています。とりわけ、水泳の授業などで感じるようです。私が親御さんに推奨しているのは、この苦痛を真剣に受け止めることです。お子さんが苦痛を感じていたり、こういった社会的状況を不安に思っている、という理由で介入（手術）を考えるであれば、正当な理由です。ですが、残念なことにそういった理由で手術に踏み切る場合、「手術で子供の肺機能が回復するのか？」という問題も避けては通れません。

And very often, a pectus will cause just a modest, a very small reduction in lung function but nothing that would cause any symptomatic problem or major limitation on exercise capacity.

非常に多くのケースで、漏斗胸が肺機能低下に及ぼす影響はごくわずかであり、自覚症状が出たり、運動能力が大きく制限されるということはないのです。

And so what I like to do is really clarify the rationale factually having a procedure done because unfortunately there's not any surgical procedure that doesn't have a potential complication and therefore parents really have to know why they're having the procedure done and the pectus is a classic example because I hear all the time from parents who say, you know, "Will it improve my child's lung function?" I've been told that he has reduced lung function or she has reduced lung capacity and I try to clarify the issue, knowing the intervention will not improve the lung function but if there's a cosmetic reason to have it done, then that's compelling.

私が望んでいるのは、現状に照らして手術をする場合の根拠を明確にするということです。なぜなら、合併症のリスクのない手術というものは存在しないからです。ですから、親御さんは手術の根拠について知っておく必要があります。漏斗胸はこういったケースでの典型例なのですが、それは私はいつも親御さんから「手術で子供の肺機能は回復するんですか？子供の肺機能や肺容量が低下しているそうですが…」という質問を受けるからです。私は手術では肺機能が回復しないということが分かっているので、手術を行う理由をはっきりさせようとします。外見上の問題だというのなら、やむを得ないと思います。

And I mean there I had an encounter a couple of years ago at one of the Marfan meetings where one of the parents was concerned about having the surgery and her son had a fairly deep pectus and brought her son into the room and we were talking about the pros and cons and I asked the son, "Are you concerned about having this pectus?" and he said, "Oh no! I think it's really cool because I can put coke cans and I could put lots of things in there when I hang out with my friends," and I asked him "Well, you know, do you feel odd because your chest is different from your friends?" and he said, "Well no, why would I want to look like everybody anyway!" and so I thought, "My gosh!" They have this exceptional child and, you know, it's wonderful. That's exactly what you want your child to say.

数年前にマルファンの会合で、かなりの深さのある漏斗胸の息子さんの手術について不安を抱えているお母さんがいました。部屋で（手術の）メリット・デメリットについてお話し、私が息子さんに「漏斗胸だと不安？」と訊くと、「全然。カッコいいと思うよ。だってコーラの缶が入るし、友達と一緒の時には色々なものを入れれるから」と彼は答えました。「友達と違う胸で変な感じしない？」「しないよ。なんでみんなと一緒じゃなきゃダメなの？」私はビックリ仰天しました。こんな子供がいるなんて。素晴らしいじゃないですか。それこそ、まさに子供に言ってもらいたい言葉です。

And because he obviously had an incredibly healthy self-concept, it didn't bother him and and so the major rationale for doing the surgery just wasn't there and I think it was very helpful for them to hear him say that in a very neutral environment and I like to encourage parents to actually have that conversation with their children.

彼は並外れて健全な自己認識を持っていたので、漏斗胸に動じることもありませんでしたし、手術の主な理由も他のところにありました。非常に公平な場で息子さんの考えを聞けたということは、ご家族にとって大きな助けとなったのではないかと思いますし、親御さんはお子さんとああいった会話をしてもらいたいと思っています。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。

マルファン患者が受けるべき肺機能試験は？

What pulmonary tests do you recommend for Marfan patients?

One of the things I actively encouraged and it almost becomes like a, like a broken record with me is I think anyone with Marfan syndrome should get a good
set of pulmonary function tests and this is for a number of reasons.

私が積極的かつ何度も繰り返し推奨しているのは、マルファン患者は適切な肺機能検査を受けるべきということです。理由はいくつかあります。

First of all, many of the organ systems that are affected in Marfan syndrome have a feature of progressive deterioration and that's one of the kind of unfortunate aspects of Marfan syndrome.

まず、残念ではありますが、マルファン症候群では多くの器官が影響を受け、次第に悪化していくという特徴があります。

Since we're unable to kind of rebuild a tissue at this point, in time, hopefully, at some point, we will, we need to kind of deal with the fact that there is going to be this accelerated course where the tissues actually become more and more vulnerable.

こうなると組織の修復はできないので、組織がますます弱まっていくという事実をどこかの時点で受けて止められるようにしておく必要があります。

In the lung, it becomes very important because many interventions are based on the determination of abnormal lung function and using kind of preventive strategies to try to avoid or delay the development of very, very severe kind of respiratory dysfunction or shortness of breath, or disability.

肺の場合、検査は非常に重要になります。なぜなら、多くの介入は異常な肺機能を特定することで行われ、非常に重篤な肺の機能不全、息切れ、肺障害の進行を避けたり、遅らせるための予防戦略を用いるためです。

And so what I suggest is that we get pulmonary function tests and these are typically tests that tell us what the capacity of someone is. Someone has to have to take a deep breath in and to blow that breath out efficiently and those studies are usually able to be conducted in children over the age of about five.

ですから、私は肺機能検査を受けることを推奨してます。この検査では、通常、肺容量を調べます。患者さんは、深呼吸した後、息をすべて吐き切ります。5歳以上であれば、たいていこの検査を受けられます。

Now, there are certain ancillary studies that go along with pulmonary function tests that aren't necessarily conducted all the time and I encourage them to be conducted to Marfan patients and these are studies of respiratory muscle strength and they include what we call maximal expiratory pressure and maximal inspiratory pressure and what they'll do is they'll tell us how of the respiratory or the breathing limitations are caused by just generalized muscle weakness

肺機能検査に付随して行われる検査もありますが、必ずしも行われるという訳ではありません。マルファン患者さんには受けることをおすすめしています。付随検査は、呼吸筋の筋力を測定する検査で、最大呼気圧と最大吸気圧を計測します。全体的な筋肉の弱体化により、どれほど呼吸機能が障害されているかを調べます。

And lastly I asked that they have, we call, a sniff fluoroscopy that sounds like a weird term, but it's basically a way of looking at the diaphragm which is a respiratory muscle and determining whether the diaphragm is actually moving appropriately and one way that we can do that is by having people sniff because the diaphragm presumably should move down when you sniff and then when the sniff is over, it'll come back up.

最後になりますが、sniff fluoroscopyと呼ばれている検査があります。呼吸筋の一種である横隔膜を調べ、動きに問題が無いことを確認します。患者さんに鼻から空気を吸い込んでもらいます。その際横隔膜は下がります。吸い込みをやめると横隔膜は元に戻ります。

And so these battery of studies can give us kind of a narrative of how the lungs are performing when they have very various tests of their function and so that's why I think they're very useful.

これらの検査を組み合わせて行うことで、肺機能を調べることができます。ですから、肺の検査は非常に重要になるのです。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。

マルファン症候群による肺への影響は？

How are the lungs affected in Marfan syndrome?

You know, the way I like to kind of discuss them are from the, the features that are the most common to the features, that are a little less common and a little more exotic.

最もよく見られる所見、あまり一般的でない所見、珍しい所見についてお話したいと思います。

And so the most common kind of respiratory manifestation of Marfan syndrome involves a chest wall and most patients with Marfan syndrome are very familiar with kind of the chest wall abnormalities, which include like pectus abnormalities; pectus excavatum where you have the sunken in chest, or carinatum where the chest actually is very prominent, and scoliosis which is curvature of the spine.

マルファン症候群で最もよく見られる呼吸器の所見は胸壁に現れます。マルファン患者のほとんどが胸壁の異常を認めます。例えば、胸が陥没する漏斗胸、胸が突出する鳩胸、そして背骨が湾曲する側弯症などです。

And lastly you can have a respiratory muscle, kind of this function and respiratory muscle weakness and that's because the skeletal muscles in patients with Marfan syndrome are decidedly weaker than the skeletal muscles and patients who don't have the syndrome.

さらに、呼吸筋に関する所見があります。マルファン患者の骨格筋は健常者と比べると確実に脆弱であるため、呼吸筋の機能も低下しています。

And so the respiratory muscle weakness and some of these chest wall abnormalities serve to reduce the respiratory capacity of the lungs and so what happens is, what we call, a restrictive defect and so the chest is largely restricted and that you can't take as deep a breath as you need in order to bring in the oxygen but also to get rid of carbon dioxide which the body normally makes.

呼吸筋の脆弱性や胸壁の異常により、肺の呼吸機能が低下し、いわゆる拘束性障害が起きます。胸部が大きな制限を受け、必要な酸素の取り込みや不要な二酸化炭素の排出ができるだけの深い呼吸ができなくなるのです。

Now well, one of the things that I notice and, you know, I focus on with parents especially, is an awareness of when kind of an abnormality develops in the context of kind of a child's normal developmental life. Now those of us who are lung specialists, we
think about the longest forming from before birth up until about the age of five or six years of age and so any type of disturbance in the thoracic cage or, what we call, the chest cage will actually translate into abnormal formation of the lung and so any child
with Marfan syndrome who has scoliosis or a pectus abnormality before that time is actually definitely going to have some sequelae in terms of lung function.

私がご両親に特にお伝えしたいのが、子供の成長過程のどの時期に症状が進行するかということですが、我々肺の専門医は、最長形成期である出生前から5、6歳までだと考えています。（この時期に発症する）胸郭のいかなる異常も、実際肺の異常形成に繋がります。ですから、この時期以前に、側弯症や胸部の異常の認められるマルファン症候群の子供は、肺機能に関して後に症状が出てくることは間違いありません。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。

マルファン症候群が肺に影響を与える理由

Why does Marfan syndrome affect the lungs?

Well, the striking aspect of lung function in Marfan syndrome is that it's so varied and it involves multiple different organ systems and the way that, I typically think about it, is that the the mutant gene of Marfan syndrome; fibrillin-1 expressed in lots and lots of different tissues and many of the cell types that is expressed in are in the lung and so the result of that is that you get abnormalities in kind of the skeletal muscle system which involves a thoracic cage. In the muscles which also involve a thoracic cage, and actually within the lung proper, which obviously is within the thoracic cage, and so all of those systems actually can be affected in Marfan syndrome.

マルファン症候群が肺機能に及ぼす影響は多岐に渡りますが、これこそが顕著な所見ということになります。マルファン症候群は複数の異なる臓器に関係し、非常に多くの異なる組織でフィブリリン-1という遺伝子の変異が発現します。肺にもそういった変異型の細胞が多く含まれ、結果として、胸郭などの骨格筋系の異常が発生します。胸郭を囲む筋肉および胸郭内にある肺そのものは、マルファン症候群の影響を受けるのです。

OK, the lung tissue itself, some of this information we've garnered from the animal models that I worked on with Hal Dietz at Johns Hopkins.

では、肺組織そのものについてお話したいと思いますが、ジョンズ・ホプキンス大学のハル・ディーツ医師との、動物モデルを使った共同研究の結果も含まれます。

And one thing we found was that the fibrillin, protein, which is the the protein that is made by the mutant gene in Marfan syndrome, is actually critical for the normal formation of the air spaces in the lungs and, as most people know, that air spaces are the sites where oxygen moves from the lung into the bloodstream.

我々が発見したのは、マルファン症候群では変異した遺伝子から作られることになる、フィブリリンと呼ばれるタンパク質は、肺内部の気腔を正常に形成するために決定的な役割を果たしているということです。ほとんどの皆さんがご存知かと思いますが、気腔というのは酸素が肺から血流へと流れ込む場所です。

And we found that these were not formed properly in mice that had the mutation in Marfan syndrome that we see in patients and so the sequelae of this is that you have under-formed or what we consider immature lungs that are unable to function properly and might not deliver the requisite amount of oxygen to the tissues.

我々の発見では、マルファン症候群のマウスでは気腔が正常に形成されていませんでした。これはマルファン患者に見られる所見です。これはマルファン症候群では後々十分な量の酸素を各組織に運ぶことのできない機能不全の肺となる可能性があるということなのです。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。

子どもがマルファンになったのは私のせいですか？

Did I do something to cause my child to have Marfan syndrome?

So when parents come in and their child is the first person in the family to have Marfan syndrome, they start replaying in their head every drink they had, you know, what they did in their teenage years and their young adult years and we really assuage their guilt; there is nothing that you did that caused this.

お子さんが家族で初めてのマルファン患者となった場合、病院にいらしたご両親は、飲んだお酒の種類や若かりし頃の行為に思いを巡らすのですが、そういったことはマルファン症候群の発症とは関係がないということをお話しし、お二人の罪悪感を和らげるようにします。

It is a random change in the DNA that happened when the egg and the sperm came together and that you have no control over how your DNA gets replicated.

原因は精子と卵子が出会った際にDNAに生じたランダムな変化であり、DNAの複製過程をコントロールすることはできないのです。

So, we try to take away that guilt as much as possible and that's a process for parents to go through but there is nothing that they did to cause Marfan syndrome in their child.

ですから私達は可能な限り、そうした罪悪感を取り去ろうと努力します。このプロセスはご両親が乗り越えなければならないものですが、子どもがマルファン症候群になった原因はご両親にはありません。

As the DNA gets replicated and gets passed down and sometimes that machinery just makes a mistake. Every single person carries about six to ten gene changes in all of their DNA and in some people, it's just in a gene that impacts your body more than in other genes and so in individuals with Marfan syndrome, the way that, that machinery replicated the DNA from their parents a simple mistake was made and it happened to be in the Marfan gene.

DNAが複製され、子どもへと受け継がれる過程でエラーが発生することがあります。誰であれ、DNAに6～10ほどの遺伝子変化があります。その変化が身体に影響を与える遺伝子に多く発生する人もいます。マルファン患者では、親のDNAが複製される過程で単純なエラーが発生しているのですが、発生場所が偶然マルファン遺伝子だったということなのです。

The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundationは、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.orgにアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。