The dual (ET and ET) endothelin receptor antagonist bosentan was approved in 2001. Sitaxentan (Thelin) was approved for use in Canada, Australia, and the European Union, but not in the United States. In 2010, Pfizer withdrew Thelin worldwide because of fatal liver complications. A similar drug, ambrisentan is marketed as Letairis in the U.S. by Gilead Sciences.

The U.S. FDA approved sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved tadalafil, another PDE5 inhibitor, marketed under the name Adcirca. PDE5 inhibitors are believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance.

Tadalafil is taken orally, as well as sildenafil, and it is rapidly absorbed (serum levels are detectable at 20 minutes). The T (biological half-life) hovers around 17.5 hours in healthy subjects. Moreover, if we consider pharmacoeconomic implications, patients that take tadalafil would pay two-thirds of the cost of sildenafil therapy. However, there are some adverse effects of this drug such as headache, diarrhea, nausea, back pain, dyspepsia, flushing and myalgia.

Pulmonary embolism may be preventable in those with risk factors. People admitted to hospital may receive preventative medication, including unfractionated heparin, low molecular weight heparin (LMWH), or fondaparinux, and anti-thrombosis stockings to reduce the risk of a DVT in the leg that could dislodge and migrate to the lungs.

Following the completion of warfarin in those with prior PE, long-term aspirin is useful to prevent recurrence.

In those with underlying heart disease, effective control of congestive symptoms prevents pulmonary edema.

Dexamethasone is in widespread use for the prevention of high altitude pulmonary edema. Sildenafil is used as a preventive treatment for altitude-induced pulmonary edema and pulmonary hypertension, the mechanism of action is via phosphodiesterase inhibition which raises cGMP, resulting in pulmonary arterial vasodilation and inhibition of smooth muscle cell proliferation. While this effect has only recently been discovered, sildenafil is already becoming an accepted treatment for this condition, in particular in situations where the standard treatment of rapid descent has been delayed for some reason.

Following diagnosis, mean survival of patients with PPH is 15 months. The survival of those with cirrhosis is sharply curtailed by PPH but can be significantly extended by both medical therapy and liver transplantation, provided the patient remains eligible.

Eligibility for transplantation is generally related to mean pulmonary artery pressure (PAP). Given the fear that those PPH patients with high PAP will suffer right heart failure following the stress of post-transplant reperfusion or in the immediate perioperative period, patients are typically risk-stratified based on mean PAP. Indeed, the operation-related mortality rate is greater than 50% when pre-operative mean PAP values lie between 35 and 50 mm Hg; if mean PAP exceeds 40-45, transplantation is associated with a perioperative mortality of 70-80% (in those cases without preoperative medical therapy). Patients, then, are considered to have a high risk of perioperative death once their mean PAP exceeds 35 mm_Hg.

Survival is best inferred from published institutional experiences. At one institution, without treatment, 1-year survival was 46% and 5-year survival was 14%. With medical therapy, 1-year survival was 88% and 5-year survival was 55%. Survival at 5 years with medical therapy followed by liver transplantation was 67%. At another institution, of the 67 patients with PPH from 1652 total cirrhotics evaluated for transplant, half (34) were placed on the waiting list. Of these, 16 (48%) were transplanted at a time when 25% of all patients who underwent full evaluation received new livers, meaning the diagnosis of PPH made a patient twice as likely to be transplanted, once on the waiting list. Of those listed for transplant with PPH, 11 (33%) were eventually removed because of PPH, and 5 (15%) died on the waitlist. Of the 16 transplanted patients with PPH, 11 (69%) survived for more than a year after transplant, at a time when overall one-year survival in that center was 86.4%. The three year post-transplant survival for patients with PPH was 62.5% when it was 81.02% overall at this institution.

Anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, may be required. People are often admitted to hospital in the early stages of treatment, and tend to remain under inpatient care until the INR has reached therapeutic levels. Increasingly, however, low-risk cases are managed at home in a fashion already common in the treatment of DVT. Evidence to support one approach versus the other is weak.

In general, the treatment of PPH is derived from the treatment of pulmonary hypertension. The best treatment available is the combination of medical therapy and liver transplantation.

The ideal treatment for PPH management is that which can achieve pulmonary vasodilatation and smooth muscle relaxation without exacerbating systemic hypotension. Most of the therapies for PPH have been adapted from the primary pulmonary hypertension literature. Calcium channel blockers, b-blockers and nitrates have all been used – but the most potent and widely used aids are prostaglandin (and prostacyclin) analogs, phosphodiesterase inhibitors, nitric oxide and, most recently, endothelin receptor antagonists and agents capable of reversing the remodeling of pulmonary vasculature.

Inhaled nitric oxide vasodilates, decreasing pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) without affecting systemic artery pressure because it is rapidly inactivated by hemoglobin, and improves oxygenation by redistributing pulmonary blood flow to ventilated areas of lung. Inhaled nitric oxide has been used successfully to bridge patients through liver transplantation and the immediate perioperative period, but there are two significant drawbacks: it requires intubation and cannot be used for long periods of time due to methemoglobinemia.

Prostaglandin PGE1 (Alprostadil) binds G-protein linked cell surface receptors that activate adenylate cyclase to relax vascular smooth muscle. Prostacyclin – PGI2, an arachadonic acid derived lipid mediator (Epoprostenol, Flolan, Treprostenil) – is a vasodilator and, at the same time, the most potent inhibitor of platelet aggregation. More importantly, PGI2 (and not nitrous oxide) is also associated with an improvement in splanchnic perfusion and oxygenation. Epoprostenol and ilioprost (a more stable, longer acting variation) can and does successfully bridge for patients to transplant. Epoprostenol therapy can lower PAP by 29-46% and PVR by 21-71%., Ilioprost shows no evidence of generating tolerance, increases cardiac output and improves gas exchange while lowering PAP and PVR. A subset of patients does not respond to any therapy, likely having fixed vascular anatomic changes.

Phosphodiesterase inhibitors (PDE-i) have been employed with excellent results. It has been shown to reduce mean PAP by as much as 50%, though it prolongs bleeding time by inhibiting collagen-induced platelet aggregation. Another drug, Milrinone, a Type 3 PDE-i increases vascular smooth muscle adenosine-3,5-cyclic monophosphate concentrations to cause selective pulmonary vasodilation. Also, by causing the buildup of cAMP in the myocardium, Milrinone increases contractile force, heart rate and the extent of relaxation.

The newest generation in PPH pharmacy shows great promise. Bosentan is a nonspecific endothelin-receptor antagonist capable of neutralizing the most identifiable cirrhosis associated vasoconstrictor, safely and efficaciously improving oxygenation and PVR, especially in conjunction with sildenafil. Finally, where the high pressures and pulmonary tree irritations of PPH cause a medial thickening of the vessels (smooth muscle migration and hyperplasia), one can remove the cause –control the pressure, transplant the liver – yet those morphological changes persist, sometimes necessitating lung transplantation. Imatinib, designed to treat chronic myeloid leukemia, has been shown to reverse the pulmonary remodeling associated with PPH.

The initial management of pulmonary edema, irrespective of the type or cause, is supporting vital functions. Therefore, if the level of consciousness is decreased it may be required to proceed to tracheal intubation and mechanical ventilation to prevent airway compromise. Hypoxia (abnormally low oxygen levels) may require supplementary oxygen, but if this is insufficient then again mechanical ventilation may be required to prevent complications. Treatment of the underlying cause is the next priority; pulmonary edema secondary to infection, for instance, would require the administration of appropriate antibiotics.

Standard medical treatment consists of anticoagulants (blood thinners), diuretics, and oxygen. Lifelong anticoagulation is recommended, even after PEA. Routine inferior vena cava filter placement is not recommended.

In patients with non-operable CTEPH or persistent/recurrent PH after PEA, there is evidence for benefit from pulmonary vasodilator drug treatment. The microvascular disease component in CTEPH has provided the rationale for off-label use of drugs approved for PAH. Currently, only riociguat (a stimulator of soluble guanylate cyclase) is approved for treatment of adults with inoperable CTEPH or persistent or recurrent CTEPH after surgical treatment. Other drug trials are ongoing in patients with inoperable CTEPH, with macitentan recently proving efficacy and safety in MERIT

Decision making for patients with CTEPH can be complex and needs to be managed by CTEPH teams in expert centres. CTEPH teams comprise cardiologists and pulmonologists with specialist PH training, radiologists, experienced PEA surgeons with a significant caseload of CTEPH patients per year and physicians with percutaneous interventional expertise. Currently, there are three recognised targeted treatment options available: pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and pulmonary vasodilator drug treatment for inoperable patients.

Specialist imaging using either magnetic resonance or invasive PA is necessary to determine risks and benefits of interventional treatment with PEA or BPA.

The incidence of clinical HAPE in unacclimatized travelers exposed to high altitude (~) appears to be less than 1%. The U.S. Army Pike's Peak Research Laboratory has exposed sea-level-resident volunteers rapidly and directly to high altitude; during 30 years of research involving about 300 volunteers (and over 100 staff members), only three have been evacuated with suspected HAPE.

The standard and most important treatment is to descend to a lower altitude as quickly as possible, preferably by at least 1000 metres. Oxygen should also be given if possible. Symptoms tend to quickly improve with descent, but more severe symptoms may continue for several days. The standard drug treatments for which there is strong clinical evidence are dexamethasone and nifedipine. Phosphodiesterase inhibitors such as sildenafil and tadalafil are also effective but may worsen the headache of mountain sickness.

Management has generally been reported to be conservative, though deaths have been reported.

- Removal from water

- Observation

- Diuretics and / or Oxygen when necessary

- Episodes are generally self-limiting in the absence of other medical problems

Treatments for primary pulmonary hypertension such as prostacyclins and endothelin receptor antagonists can be fatal in people with PVOD due to the development of severe pulmonary edema, and worsening symptoms after initiation of these medications may be a clue to the diagnosis of pulmonary veno occlusive disease.

The definitive therapy is lung transplantation, though transplant rejection is always a possibility, in this measures must be taken in terms of appropriate treatment and medication.

It is sometimes treated with surgery, which involves rerouting blood from the right atrium into the left atrium with a patch or use of the Warden procedure. However, interest is increasing in catheter-based interventional approaches, as well as medical therapy for less severe cases.

Pulmonary venoocclusive disease is rare, difficult to diagnose, and probably frequently misdiagnosed as idiopathic pulmonary arterial hypertension. Prevalence in parts of Europe is estimated to be 0.1-0.2 cases per million.

PVOD appears to occur as frequently in men as in women, and age at diagnosis ranges from 7–74 years with a median of 39 years. PVOD may occur in patients with associated diseases such as HIV, bone marrow transplantation, and connective tissue diseases. PVOD has also been associated with several chemotherapy regimens such as bleomycin, BCNU, and mitomycin.

Death may occur rapidly with acute, massive pulmonary bleeding or over longer periods as the result of continued pulmonary failure and right heart failure. Historically, patients had an average survival of 2.5 years after diagnosis, but today 86% may survive beyond five years.

Usually the sequestration is removed after birth via surgery. In most cases this surgery is safe and effective; the child will grow up to have normal lung function.

In a few instances, fetuses with sequestrations develop problematic fluid collections in the chest cavity. In these situations a Harrison catheter shunt can be used to drain the chest fluid into the amniotic fluid.

In rare instances where the fetus has a very large lesion, resuscitation after delivery can be dangerous. In these situations a specialized delivery for management of the airway compression can be planned called the EXIT procedure, or a fetal laser ablation procedure can be performed. During this minimally invasive fetal intervention, a small needle is inserted into the sequestration, and a laser fiber is targeted at the abnormal blood vessel going to the sequestration. The goal of the operation is to use laser energy to stop the blood flow to the sequestration, causing it to stop growing. Ideally, after the surgery, the sequestration steals less blood flow from the fetus, and the heart and lungs start growing more normally as the sequestration shrinks in size and the pleural effusion goes away.

The treatment for this is a wedge resection, segmentectomy, or lobectomy via a VATS procedure or thoracotomy.

Pulmonary sequestrations usually get their blood supply from the thoracic aorta.

Most of the medical literature on the topic comes from case series in military populations and divers, and an epidemiological study in triathletes. A recent experimental study showed increased pulmonary artery pressure with cold water immersion, but this was done in normal subjects rather than in people with a history of SIPE. A study in SIPE-susceptible individuals during submersion in cold water showed that pulmonary artery and pulmonary artery wedge pressures were higher than in non-susceptible people. These pressures were reduced by sildenafil. SIPE may also be a cause of death during triathlons.

Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which, in turn, can lead to heart failure of the right ventricle. Hypoxia can be prevented with oxygen supplementation.

Pulmonary fibrosis may also result in an increased risk for pulmonary emboli, which can be prevented by anticoagulants.

Pulmonary fibrosis creates scar tissue. The scarring is permanent once it has developed. Slowing the progression and prevention depends on the underlying cause:

- Treatment options for idiopathic pulmonary fibrosis are very limited. Though research trials are ongoing, there is no evidence that any medications can significantly help this condition. Lung transplantation is the only therapeutic option available in severe cases. Since some types of lung fibrosis can respond to corticosteroids (such as prednisone) and/or other medications that suppress the body's immune system, these types of drugs are sometimes prescribed in an attempt to slow the processes that lead to fibrosis.

- Two pharmacological agents intended to prevent scarring in mild idiopathic fibrosis are pirfenidone, which reduced reductions in the 1-year rate of decline in FVC. Pirfenidone also reduced the decline in distances on the 6-minute walk test, but had no effect on respiratory symptoms. The second agent is nintedanib, which acts as antifibrotic, mediated through the inhibition of a variety of tyrosine kinase receptors (including platelet-derived growth factor, fibroblast growth factor, and vascular endothelial growth factor). A randomized clinical trial showed it reduced lung-function decline and acute exacerbations.

- Anti-inflammatory agents have only limited success in reducing the fibrotic progress. Some of the other types of fibrosis, such as non-specific interstitial pneumonia, may respond to immunosuppressive therapy such as corticosteroids. However, only a minority of patients respond to corticosteroids alone, so additional immunosuppressants, such as cyclophosphamide, azathioprine, methotrexate, penicillamine, and cyclosporine may be used. Colchicine has also been used with limited success. There are ongoing trials with newer drugs such as IFN-γ and mycophenolate mofetil..

- Hypersensitivity pneumonitis, a less severe form of pulmonary fibrosis, is prevented from becoming aggravated by avoiding contact with the causative material.

- Oxygen supplementation improves the quality of life and exercise capacity. Lung transplantation may be considered for some patients.

Corticosteroids are the mainstay of treatment of IPH, though they are controversial and lack clear evidence in their favour. They are thought to decrease the frequency of haemorrhage, while other studies suggest that they do not have any effect on the course or prognosis of this disease. In either case, steroid therapy has significant side effects. Small trials have investigated the use of other medications, but none has emerged as a clear standard of care. This includes immune modulators such as hydroxychloroquine, azathioprine, and cyclophosphamide. 6-mercaptopurine as a long-term therapy may prevent pulmonary haemorrhage. A 2007 scientific letter. reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine.

Different treatments have been used to manage pulmonary interstitial emphysema with variable success. Admission/transfer to a neonatal intensive care unit (NICU) is common and expected for patients with PIE.

Treatments include:

- Lateral decubitus position with the affected side down

- High-frequency ventilation

- Lobectomy

- Selective Main Bronchial Intubation and Occlusion

Pulmonary capillary hemangiomatosis (PCH) is a disease affecting the blood vessels of the lungs, where abnormal capillary proliferation and venous fibrous intimal thickening result in progressive increase in vascular resistance. It is a rare cause of pulmonary hypertension, and occurs predominantly in young adults. Together with pulmonary veno-occlusive disease, PCH comprises WHO Group I' causes for pulmonary hypertension. Indeed, there is some evidence to suggest that PCH and pulmonary veno-occlusive disease are different forms of a similar disease process.

Pulmonary capillary hemangiomatosis patients, families, and caregivers are encouraged to join the Registry NIH Rare Lung Diseases Consortium Contact Registry

Pulmonary interstitial emphysema often resolves gradually and may take 2–3 weeks. For longer durations of PIE the length of time of mechanical ventilation needed may increase and the incidence of bronchopulmonary dysplasia becomes higher. Some infants may develop chronic lobar emphysema, which may require surgical lobectomies.