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The Four Stages of Pneumonia from Early Symptoms to Recovery

Red hepatization.

• As Pneumonia Progresses

A bout of pneumonia happens in four stages: congestion, red hepatization, grey hepatization, and resolution. The names of each stage refer to how the infection develops over time.

The initial congestion stage is characterized by a wet cough, chest pain, and fever. Symptoms usually worsen in the hepatization stages, and you may have difficulty breathing. The infection typically resolves within one to two weeks. The exact symptoms may depend on your age, overall health, and the type of germ responsible (bacterial vs. viral).

This article discusses the progression of pneumonia from early to late stages. It also touches on how these stages can differ in people who receive treatment versus those who do not.

FG Trade / Getty Images

The first stage of pneumonia is called "congestion" because it is characterized by congestion in the lungs.

Specifically, pneumonia causes the tiny air sacs in the lungs ( alveoli ), as well as tiny nearby blood vessels (capillaries), to become inflamed and congested with fluid. Most of this congestion takes place during the first 24 hours after the infection develops.

As you breathe, an exchange of oxygen and carbon dioxide takes place between the capillaries and the alveoli. Since these are the primary structures affected by pneumonia, you will start to notice more breathing-related symptoms as the infection progresses.

Fortunately, when pneumonia is detected and promptly treated during the congestion stage, it is less likely to result in complications. However, the severity of the infection depends on several factors, including your age, overall health, and whether the infection is bacterial or viral.

Lobar pneumonia, caused by bacterial infection, is pneumonia that affects one section (lobe) of the lungs. It's more common than the other form of pneumonia—viral pneumonia—which is caused by viruses.

The congestion stage of pneumonia may start suddenly or gradually. Symptoms may be especially severe when pneumonia develops as a complication of another infection, such as influenza or COVID-19.

Symptoms in the congestion stage may include:

• Coughing, which may produce sputum that is clear, yellow, or green
• High fever and chills
• Chest pressure or heaviness
• Sharp chest pain that worsens with deep breaths ( pleuritic chest pain )
• Shortness of breath
• Loss of appetite
• Muscle aches ( myalgia )
• Joint aches ( arthralgia )

Some people may develop hypoxia (reduced oxygen level in the body) in the early stages of the infection. Symptoms include:

• A bluish tinge to the lips and fingers (cyanosis)
• Rapid respiratory rate ( tachypnea )
• Rapid heart rate ( tachycardia )
• Disorientation
• Shortness of breath ( dyspnea )

In some cases, symptoms of hemoptysis ( coughing up blood ) may occur, even at the onset of the infection. This can be very alarming and warrants immediate medical attention in any case.

Children often experience many of the same symptoms as adults. However, in some cases the only symptom a child has is rapid breathing. Children may also develop a lack of appetite, which can lead to dehydration.

Stage 1 Symptoms in the Elderly

In older adults, typical symptoms (such as a fever or cough) may be absent, and instead, the only symptoms may be confusion or falls.

Management/Treating Symptoms

Once diagnosed, antibiotics should be started almost immediately. Blood cultures (blood tests done to see if bacteria are present in the blood) are often done. If the infection is found to be bacterial, then antibiotic treatment will likely be started right away.

Depending on the severity, hospital admission or intensive care unit (ICU) admission may be needed. This is especially true if a person has hypoxia or difficulty breathing.

In the hospital, pulse oximetry is usually used to monitor oxygen levels continually via a small pulse oximeter device placed on the finger. Intravenous (IV) fluids may also be needed. If oxygen saturation is below 92% on oximetry, oxygen therapy may be needed, even this early in the infection.

When antibiotics are started promptly following early signs of infection, the fever may resolve within 48 to 72 hours.

Complications

The most common complication of early pneumonia (that may necessitate hospitalization) is a low oxygen level. Depending on the severity, oxygen supplementation may be needed, as well as admission to the ICU.

After the initial 24 hours, symptoms of pneumonia may worsen as red blood cells and other immune cells rush to the lungs and alveoli to fight the infection. This stage, known as red hepatization, occurs about two to three days after the infection develops.

As red blood cells fill the lungs, the lungs, which are normally pinkish-gray in color, literally become flushed with red. Reduced oxygen levels also cause the lungs to become dry and firm, much like a liver. The term "hepatization" refers to this liver-like appearance.

During red hepatization, symptoms are usually more severe even if treatment has been started. These can include:

• Coughing that produces thick, yellow-green, and sometimes blood-stained phlegm
• Fever, chills, and rigors (violent shivering)
• Severe shortness of breath
• Muscle aches
• Cyanosis, in which the lips and fingers appear blue or even blackish due to low oxygen
• Extreme fatigue

In older adults, confusion or delirium may appear even despite oxygen therapy.

The Importance of Respiratory Rate

The most useful sign as to severity at this stage is the respiratory rate (in people who do not have preexisting lung disease). A respiratory rate greater than 30 breaths per minute often means that hospitalization in intensive care is needed.

Managing/Treating Symptoms

During this stage of the infection, antibiotics are continued (intravenously if in the hospital) or started if a person has not yet been evaluated. For those diagnosed early, blood cultures may come back from the lab indicating the particular bacteria (if it is a bacterial pneumonia) responsible.

Knowing the type of bacteria present may lead physicians to change your treatment to a more appropriate or specific antibiotic. Sensitivities (tests that determine which antibiotic is most effective for the bacteria isolated) may also be returned and further guide appropriate therapy.

Oxygen may be started at this point or continued in those who already have low oxygen levels. In some cases, oxygen alone may be insufficient. A first step may be to use noninvasive positive pressure ventilation such as CPAP (continuous positive airway pressure). Positioning may also help, as lying in the prone position (on the stomach) can maximize the surface area of the lungs available to absorb oxygen.

If low oxygen levels persist, or if there is evidence that organs of the body are not getting enough oxygen (such as kidney dysfunction), insertion of an endotracheal tube and mechanical ventilation may be needed.

Additional testing may be needed if complications are suspected.

Complications may appear at any point with a diagnosis of pneumonia, but red hepatization is often when people appear most ill.

Bacteria that are present in the lungs may spread in the bloodstream ( bacteremia ) and then travel to other regions of the body. With pneumococcal pneumonia, up to 25% to 30% of people will have bacteremia.

With bacteremia, bacteria can travel to and infect other bodily organs, including:

• The brain ( meningitis )
• Heart valves (endocarditis)
• The lining of the heart (pericardium)
• Joints (septic arthritis)

Septicemia and Sepsis

Septicemia , also called blood poisoning, may occur at any stage. While bacteremia refers to the presence of bacteria in the bloodstream, septicemia refers to a state in which bacteria are multiplying in the bloodstream. With septicemia, a person will appear extremely ill, often with a very rapid pulse and confusion.

In contrast to septicemia, sepsis refers to the body's response to bacteria in the bloodstream. This overwhelming response of the immune system is very critical. Even with medications to raise blood pressure (which is often very low) and counteract the intense inflammatory response, sepsis is often fatal. Significant research is focusing on ways to prevent sepsis from occurring.

Since lobar pneumonia often extends to the lung lining (pleura), inflammation can result in the buildup of fluid between these membranes (a pleural effusion ). In some cases, pus may build up and accumulate between the pleural membranes, a complication known as an empyema .

The most common causes include Streptococcus pneumoniae (the most common cause of bacterial pneumonia) and Staphylococcus . Symptoms are similar to pneumonia itself, with a cough, fever, chest pain, and shortness of breath, so doctors must be alert for this complication. If a significant pleural effusion is seen on imaging, further workup is often needed.

When an empyema is present, a thoracentesis is often the next step. This involves inserting a long, thin needle through the skin and into the pleural space to obtain a sample of the fluid. The sample can then be looked at in the lab to visualize any bacteria present and to do a culture of the fluid.

If a large empyema is present, a chest tube may need to be placed. This involves inserting a somewhat larger tube into the pleural space that is left in place and connected to continuous suction to remove the fluid.

In children and infants, especially those who have pneumonia due to Staphylococcus aureus , an empyema may occur. Severe infections may also result in the collapse of the lung ( pneumothorax ) and pneumatoceles (air-filled cysts within the lungs).

What are the Last Stages of Pneumonia Before Death?

End-stage pneumonia typically involves severe respiratory distress, requiring supplemental oxygen. Signs of oxygen deprivation, such as blue skin and an altered mental state, are usually apparent. Sepsis followed by multiple organ failure may occur and quickly lead to death.

Grey Hepatization

The third stage of pneumonia, known as grey hepatization, sets in about four to six days after the infection develops. During this stage, red blood cells begin to break up, causing the lungs to become greyish-brown or yellow in color. The lungs will become drier, too, further taking on a liver-like consistency.

During grey hepatization, many of the same symptoms experienced in red hepatization will persist. Breathing may become especially difficult, necessitating additional oxygen therapy or mechanical ventilation. Fits of coughing may become more severe and produce blood.

During grey hepatization, antibiotics (for bacterial pneumonia) will be continued. For those who are improving and in the hospital, intravenous antibiotics may be exchanged for oral antibiotics.

If complications have occurred, treatments to address these complications may continue, such as a chest tube to manage an empyema, and corticosteroids if an intense immune response is present.

Oxygen or other types of breathing assistance may continue, be stopped, or instead be initiated for the first time.

For those who are hospitalized, attention to other complications, such as dehydration, kidney dysfunction, and more, will require careful monitoring and management.

Complications noted in the earlier stages of pneumonia may not occur until grey hepatization for some people, especially those who have not received treatment.

For those who have a severe infection, a lung abscess may form.

In addition to symptoms associated with pneumonia—such as fever and cough—other symptoms of a lung abscess can include:

• An increase in sputum that can become foul-smelling
• Worsening of cough and fever, if they had been improving
• Night sweats (drenching sweats that require getting up and changing pajamas) can occur
• Weight loss in those who develop an abscess some time after their pneumonia occurred
• Coughing up blood (quite common)

An abscess itself can also lead to further complications, such as:

• An empyema (if not already present)
• A bronchopleural fistula (an abnormal passageway between the bronchi and the pleural cavity)
• Bleeding into the lungs

Treatment begins with broad-spectrum antibiotics (a lung abscess will usually require a change in antibiotics being used). If this is ineffective, the abscess may need to be drained (often with a long, narrow needle inserted through the skin).

In some cases, surgical removal of the abscess will be needed. Follow-up is also very important, as underlying lung cancer has been found in one to two out of 10 lung abscesses.

What Are the Worst Days of Pneumonia?

Pneumonia can be unpredictable and complications may occur at any time. In most cases, pneumonia peaks during the hepatization stages, in which the risk of hypoxia (low oxygen) and severe complications is particularly high. Research shows the mortality rate for people with pneumonia placed in the ICU (intensive care unit) is approximately 15% to 50%.

The final stage of pneumonia, known as resolution, depends on how quickly treatment was started. Ordinarily, resolution of the infection occurs around eight days after the start of the infection.

In children, it can take two to three weeks for mild pneumonia to resolve, or up to eight weeks for pneumonia that is severe.

This recovery stage includes:

• Resolution of the infection
• Restoration of the normal airways and alveoli

At this point in the infection, the immune system works to repair the damage to the lungs. This includes the release of enzymes that break down damaged tissue so that it can be reabsorbed. An influx of cells called macrophages will travel through the lungs and "eat" ( phagocytize ) debris and white cells containing bacteria.

Leftover debris in the lungs that can't be eliminated in this way is usually coughed up.

Since debris in the lungs that can't otherwise be removed is coughed up, a cough productive of sputum is very common at this stage. Knowing that the body is continuing to repair damage that was done during the infection can help explain the fatigue often present (and why rest is still important).

If untreated (and in some cases even with treatment), respiratory symptoms may worsen, When treatment is started early, however, and no serious complications have occurred, symptoms usually improve significantly at this point in time (except for the cough).

If scar tissue develops in the pleura (pleural adhesions), pain with a deep breath may occur and may last for quite some time.

Antibiotics are usually continued for at least 10 days. If antibiotics were previously given intravenously, they may be changed to oral tablets. For those who were hospitalized, many can be discharged (if not discharged already).

For those who continue to worsen, oxygen or mechanical ventilation may need to be started at this time. In some cases, oxygen therapy will be needed long-term. On the other hand, those who were on supplemental oxygen, but whose condition is improving, can start to be weaned off of oxygen therapy.

Complications discussed at other stages may occur later in the infection, especially lung abscesses.

The repair process may result in scar tissue in the lung linings (pleural adhesions) that may affect care in the future. For example, it could cause problems with pleural effusions or lung cancer surgery down the road.

Roughly 10% to 15% of people will have a recurrent episode of pneumonia within two years of the infection.

For some people, lung damage may persist, requiring long-term oxygen supplementation. Severe pneumonia may also worsen underlying chronic obstructive pulmonary disease (COPD).

How Can You Tell if Pneumonia Is Getting Better or Worse?

Most people with pneumonia start to feel better within a few days of starting treatment with antibiotics. It is a good sign that you are recovering if your temperature returns to normal within seven days. You should be coughing less, breathing better, and feeling less chest pressure as time goes on. Contact your healthcare provider if this isn't the case.

Pneumonia, which can be viral or bacterial in origin, occurs in four stages: congestion, red hepatization, grey hepatization, and resolution. The names of each stage refer to how the infection affects the lungs. While congestion often manifests with flu-like symptoms, the hepatization stages tend to be marked by worsening breathing difficulties and a greater risk for complications.

The body works hard to repair the lungs during the resolution stage, but there may still be long-term lung damage. Many people with pneumonia require supplemental oxygen at various stages of the infection; for some, oxygen therapy will be needed long-term.

A Word From Verywell

While pathologists have accurately described the four stages of pneumonia as discussed here, clinicians taking care of patients focus more on the patient's progressing symptoms and vital signs as they work to provide the antibiotics and ongoing supportive care needed to help the body fight off the underlying infection and inflammation. For the clinician, the "stages" of pneumonia are more likely to take the form of "worsening, stabilizing, and resolving."

National Heart, Lung, and Blood Institute. Pneumonia - Recovery .

Torres A, Cilloniz C, Niederman M, et al. Pneumonia . Nat Rev Dis Primers . 2021 Apr;7(1):1-28. doi:10.1038/s41572-021-00259-0

American Lung Association. What causes pneumonia? .

Children's Hospital Colorado. Pneumonia in children .

Yale Medicine. Pulse oximetry .

Jameson JL, Fauci AS, Kasper KL, et al (Eds.). Harrison's Principles of Internal Medicine . McGraw-Hill Education.

American Lung Association. Pneumonia symptoms and diagnosis .

BASS Primary Care. Four stages of pneumonia .

Centers for Disease Control and Prevention. Pneumococcal disease. Clinical features .

Polat G, Anil Ugan R, Cadirci E, Halici Z. Sepsis and septic shock: Current treatment strategies and new approaches . Eurasian J Med . 2017 Feb;49(1):53-58. doi:10.5152/eurasianjmed.2017.17062

Godfrey MS, Bramley KT, Detterbeck F. Medical and surgical management of empyema . Semin Respir Crit Care Med.  2019;40(3):361-374. doi:10.1055/s-0039-1694699

Mercanzin E, Bonaffini P, Barletta A, et al. Pneumonia-related pneumatoceles in infants: CT assessment and image-guided treatment . BJR Case Rep . 2021 Dec;8(2):1-5. doi:10.1259/bjrcr.20210191

Kuhajda I, Zarogoulidis K, Tsirgogianni I, et al.  Lung abscess-etiology, diagnostic and treatment options .  Annals of Translational Medicine . 2015. 3(13):183. doi:10.3978/j.issn.2305-5839.2015.07.08

Li G, Cook D, Thabane L, et al. Risk factors for mortality in patients admitted to intensive care units with pneumonia . Respir Res . 2016 Jul;17(80):1-9. doi:10.1186/s12931-016-0397-5

Alberta. Pneumonia in children: Care instructions .

Broaddus VC, Mason RJ, Ernst JD, et al. Murray & Nadel’s Textbook of Respiratory Medicine . Elsevier Saunders, Philadelphia,

Cilloniz , Gabarrus A, Almirall J, et al. Bacteraemia in outpatients with community-acquired pneumonia . Eur Respir J.  2016;47(2):654-7. doi:10.1183/13993003.01308-2015

Pan F, Ye T, Sun P, et al. Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19) . Radiology . 2020;295(3):715-721. doi:10.1148/radiol.2020200370

By Lynne Eldridge, MD  Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."

Appointments at Mayo Clinic

Walking pneumonia: what does it mean, what is walking pneumonia how is it different from more serious pneumonia.

"Walking pneumonia" is an informal term for a common bacterial condition. It produces milder symptoms that appear more gradually than in other types of more serious pneumonia.

Symptoms may include:

• Sore throat.
• Runny nose.
• Chest pain from coughing.

Symptoms usually appear within two to three weeks of becoming infected and can continue for weeks. A cough could continue for months.

With walking pneumonia, you may feel like you have a cold. But symptoms are usually mild, so you likely won't need bed rest or a hospital stay. You may not feel the need to stay home from work or school. So you may be out walking around. That's how the illness got its name.

While anyone can be infected with walking pneumonia, it's most common in children, especially those ages 5 to 15 years old. This illness is often brought home by young children who get it at school and then infect family members.

Walking pneumonia is contagious. It's spread through airborne droplets from close contact, such as coughing, sneezing or speaking. People with lowered immunity may get more severely ill. You can be contagious long after you no longer have symptoms.

Your symptoms may be mild enough that you don't see a health care provider. But if you do, your health care provider is not likely to prescribe antibiotics unless you have a more serious form of pneumonia or another severe infection.

Possible complications of walking pneumonia include:

• A more serious form of pneumonia.
• Worsening of asthma symptoms.
• Swelling and irritation of the brain, known as encephalitis.
• Hemolytic anemia, a type of anemia caused by the breakdown of too many red blood cells.

To help prevent walking pneumonia, wash your hands often with soap and water for 20 seconds. If soap and water are not available, use hand sanitizer. Cover your mouth with a tissue when you cough or sneeze. If you don't have a tissue, bend your arm toward you and cough or sneeze into your elbow — not your hands.

Misbah Baqir, M.B.B.S.

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• Goldman L et al., eds. Mycoplasma pneumoniae. In: Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Dec. 19, 2022.
• Elsevier Point of Care. Mycoplasma pneumoniae infections. https://www.clinicalkey.com. Accessed Dec. 19, 2022.
• Baum S. Mycoplasma pneumoniae infection in adults. http://www.uptodate.com/contents/search. Accessed Dec. 19, 2022.
• Mycoplasma pneumoniae infections. Centers for Disease Control and Prevention. https://www.cdc.gov/pneumonia/atypical/mycoplasma/. Accessed Dec. 19, 2022.
• Coughing and sneezing. Centers for Disease Control and Prevention. https://www.cdc.gov/hygiene/personal-hygiene/coughing-sneezing.html. Accessed Dec. 21, 2022.

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Migratory pulmonary consolidation

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Citation, DOI, disclosures and article data

At the time the article was created Mohammad Taghi Niknejad had no financial relationships to ineligible companies to disclose.

At the time the article was last revised Daniel J Bell had no financial relationships to ineligible companies to disclose.

• Migratory consolidation

Migratory pulmonary consolidation , also known as wandering pulmonary consolidation , refer to air space opacities that change in location over time, and are characteristic of a subset of lung diseases.

The differential diagnoses include:

• organizing pneumonia   1
• recurrent aspiration pneumonia
• eosinophilic pneumonia   3
• pulmonary hemorrhage
• pulmonary alveolar proteinosis
• pulmonary vasculitis   4
• pulmonary infarction
• Sweet syndrome   5  - rare
• 1. Beardsley B & Rassl D. Fibrosing Organising Pneumonia. J Clin Pathol. 2013;66(10):875-81. doi:10.1136/jclinpath-2012-201342 - Pubmed
• 2. Polverosi R, Maffesanti M, Dalpiaz G. Organizing Pneumonia: Typical and Atypical HRCT Patterns. Radiol Med. 2006;111(2):202-12. doi:10.1007/s11547-006-0021-8 - Pubmed
• 3. Jeong YJ, Kim KI, Seo IJ et-al. Eosinophilic lung diseases: a clinical, radiologic, and pathologic overview. Radiographics. 27 (3): 617-37. doi:10.1148/rg.273065051 - Pubmed citation
• 4. Chung MP, Yi CA, Lee HY et-al. Imaging of pulmonary vasculitis. Radiology. 2010;255 (2): 322-41. doi:10.1148/radiol.10090105 - Pubmed citation
• 5. Raby B & Dong H. A Case of Migratory Pulmonary Infiltrates Associated With Sweet Syndrome. Chest. 2016;150(4):1063A. doi:10.1016/j.chest.2016.08.1170
• 6. Imokawa S, Yasuda K, Uchiyama H et al. Chlamydial Infection Showing Migratory Pulmonary Infiltrates. Intern Med. 2007;46(20):1735-8. doi:10.2169/internalmedicine.46.0180 - Pubmed

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What Is Walking Pneumonia?

by Editorial Staff | April 14, 2023

"Walking pneumonia" is a non-medical term for a mild case of pneumonia. A more medically correct term would be atypical pneumonia and can be caused by certain molds, viruses or bacteria; often a common bacterium called Mycoplasma pneumonia . Bed rest or hospitalization are usually not needed, and symptoms can be mild enough that you can continue your daily activities, hence the term "walking."

But don't be fooled. Walking pneumonia can still be miserable and is commonly accompanied by a cough, fever, chest pain, mild chills, headache, etc. It feels more akin to a bad cold, and despite what the term "walking" implies, taking care of yourself is the best path to recovery.

"If you have pneumonia symptoms, even if they are mild, you should discuss with your healthcare provider as soon as possible," says Dr. Albert Rizzo, American Lung Association’s Chief Medical Officer. Dr. Rizzo notes that walking pneumonia is treatable with antibiotics to help you recover more quickly if your doctor believes bacteria to be the cause. Over-the-counter medications can also be used to relieve symptoms, such as antihistamines for nasal congestion or cough medications to help ease cough and loosen any mucus (sputum). "In addition, it's important to get lots of rest, drink plenty of fluids and take fever-reducing medicine if you have a fever," he adds. Not everyone can take the same over-the-counter medications, so it is important to come up with a treatment plan with your healthcare provider’s input.

Most people start to feel better within three to five days, but a cough from pneumonia can last weeks or months after treatment. "Recovery time will vary from person to person and will depend on whether you have other medical problems, such as asthma or COPD ," says Dr. Rizzo. "Too slow a pace of recovery or any worsening of symptoms is information you should share with your healthcare provider."

Pneumonia can spread when an infected person breathes, talks, coughs or sneezes near you. To reduce your risk of infection, follow these tips and learn more about avoiding pneumonia:

• Get a flu vaccine each year to help prevent getting pneumonia caused by the flu.
• Talk to your doctor about getting a pneumonia vaccine (there is no vaccine for viral or mycoplasma pneumonia, but certain individuals should get vaccinated for pneumococcal pneumonia).
• Make sure your pertussis vaccine is up to date (speak with your healthcare provider).
• Exercise, eat a well-balanced diet and get adequate sleep.
• Wash your hands frequently and thoroughly with warm, soapy water.
• Don't smoke.
• Cover your mouth when you cough or sneeze and encourage others to as well to help prevent the spread of these infections.

Learn more about pneumonia on our website.

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Recovering from a Serious Lung Infection

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Blog last updated: October 4, 2023

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Infectious Diseases A-Z: What is walking pneumonia?

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"Walking pneumonia is caused by a type of bacteria we classify as an atypical type of bacteria," says Dr. Nipunie Rajapakse , a Mayo Clinic pediatric infectious diseases specialist. "Most commonly, that bacteria is called M ycoplasma pneumonia e ."

Watch: Dr. Nipunie Rajapakse explains walking pneumonia .

Journalists: Broadcast-quality sound bites are in the downloads.

“Symptoms of walking pneumonia are similar to symptoms of pneumonia, but generally are on the milder side," says Dr. Rajapakse. "A child or a person with this infection can experience a cough , fever , runny nose , some difficulty with breathing, occasionally chest pain or some shortness of breath, as well."

Occasionally, walking pneumonia can progress to a more severe pneumonia that may require hospitalization.

Dr. Rajapakse says, "When we talk about pneumonia, we’re referring to an infection in the lungs. Pneumonia can be caused by both bacteria and viruses and, in rare cases, fungi as well. But when we talk about pneumonia, we’re really referring to an infection of the lung tissue."

"If you think you might have walking pneumonia, or any type of pneumonia, it’s a good idea to see your physician or your primary care provider," says Dr. Rajapakse. "They will really be the best ones to do a physical examination and potentially order a chest X-ray  –if they think that one is warranted – to determine whether you might have pneumonia or not."

The Centers for Disease Control and Prevention  offers these tips to prevent the spread of infection.

• Cover your mouth and nose with a tissue when you cough or sneeze.
• Put your used tissue in the wastebasket.
• If you don't have a tissue, cough or sneeze into your upper sleeve or elbow–not your hands.
• Wash your hands often with soap and water for at least 20 seconds.
• If soap and water are not available, use an alcohol-based hand rub.
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Related Articles

Wandering Pneumonia

Affiliation.

• 1 Department of General Medicine, National Defense Medical College, Saitama, Japan.
• PMID: 37941682
• PMCID: PMC10628320
• DOI: 10.31662/jmaj.2023-0063

Keywords: IgG4-related disease; IgG4-related lung disease; Wandering pneumonia.

Publication types

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Medical Definition of Wandering pneumonia

1. A form of pneumonia in which successive areas of the lung are affected; may occur in bronchopulmonary aspergillosis. Synonym: wandering pneumonia. (05 Mar 2000)

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Opinion Why am I hiking the Appalachian Trail? It’s a matter of opportunity.

Like any big decision, dropping everything to hike with my teenager for six months just suddenly made sense.

Rusty Foster, author of the Today in Tabs newsletter, recently announced he’s pausing publication to hike the Appalachian Trail with his 19-year-old son Mica. The two plan to trek from Maine to Georgia over approximately six months, departing July 2. This is the first in a series of pieces adapted from the newsletter he will be filing from the wilderness, Today on Trail .

A number of people have asked me some version of: “Why would you leave a lovely family and a perfectly comfortable home to traverse the East Coast by foot for half a year, climbing every mountain along the way?” To answer that question, I need to share a piece of personal lore that might at first seem unrelated, but I promise I’m going somewhere with it.

The day I asked my wife to marry me, I didn’t wake up knowing that’s what would happen that day. If I could travel back in time to the year 2000 and meet myself five minutes before I proposed, young me would have been very surprised to learn that in six minutes he would be engaged.

The day we got engaged, we were in Europe, me and my future wife, touring Schloss Nymphenburg in Munich. Her parents are both originally German, though they met and settled in New York state, where Christina grew up. We were picking them up in Munich and then meeting her older siblings in Südtirol, the German-speaking part of the Italian Alps. I’m sure there are many people who knew there was a German-speaking part of the Italian Alps, but I wasn’t one of them until that trip, nor did I know there is a particularly German definition of “hiking” that involves eating a lot of bread and cold cuts and then walking a couple of kilometers uphill to an alm where you are served even more bread and cold cuts, along with heaps of wurst and shots of the most potent homemade kirsch imaginable. They uncorked that schnapps bottle and we could smell it across 200 meters of edelweiss.

But all that hadn’t happened yet. It was early August and hot and we were both dusty from wandering around the gardens of Nymphenburg, killing time in Munich before we met her parents to drive south into the mountains. I had a headache and wanted an iced coffee, so we went to the overpriced tourist cafe. I got a coffee and we sat at a wire patio table. Midafternoon, and the place was nearly empty. We were minutes from getting engaged. We chatted a bit. Seconds from getting engaged. Neither of us knew it yet.

In a way, though, we both knew it already. We had talked about getting married in general terms. I mean we’d talked about getting married to each other , so the terms weren’t all that general. No one had said “will you,” but we were in agreement that it would happen at some point. We were both 18 when we met, freshman year of college. We lived in the same dorm, her hall was directly below mine. At a freshman mixer, before classes even started, I was charmed by her Doc Martens and her long blonde hair and her glamorous stories of backpacking across Europe alone and seeing Nine Inch Nails at Woodstock ’94. She remembered a good joke I made at that mixer, but it wasn’t until we’d been married for more than a decade that she realized it was me who’d made it. I had to work a little harder to capture her attention than she did to capture mine.

In the six years that elapsed between the freshman mixer and that afternoon in the cafe, we had been together for 1½ years, then not officially together for about three years because I was callow and indecisive, and then back together for another year and a half. In all that time, though, neither of us was closer to another person than we were to each other. We knew we would be together because we’d tried being apart and it didn’t work.

That day, the conversation turned to the German relatives I would soon meet for the first time, and Christina said, “It doesn’t feel right introducing you as ‘my boyfriend.’ It sounds too casual for our actual relationship.”

This was the moment. I know I’m going to ask her soon , I thought, so if not now then when? I have no plan, no ring, but we’re in Europe! That’s inherently romantic. We would probably want to buy the ring together anyway. And this is maybe the best conversational opening I’m ever going to get. This is the moment, just do it.

“You could call me your fiancé,” I said.

“Ha ha —” she said, then she looked at my face, and said “Oh!”

I think I said the actual words, then: Will you marry me? And I think she said yes. But that part of the memory is fuzzy. What I really remember is: “ha ha … oh!” Her sudden realization that I was serious mirrored my sudden realization that this was the moment, that it had arrived seemingly out of nowhere on a day that didn’t begin with any portentous signs or omens. We secretly bought some champagne and told her parents we were engaged a few days later, on her father’s birthday, and he cried. Her mother told me that the first time she met me she didn’t like me, but that she liked me now. We bought a handmade engagement ring from a tiny jeweler’s shop in a side alley in Venice.

The point of this long anecdote with only the flimsiest connection to hiking is that I believe that life is essentially arbitrary, and the only trick to it is being in the right place at the right time. But no one knows what the right time will be, so you just have to find the right place and wait, staying alert for the right time to present itself.

Christina has always been a combination of amused and annoyed that the way we got engaged makes such a charming story, despite my seeming lack of preparation. But I’d been preparing for six years. I was so prepared that when the opportunity presented itself, I was able to recognize it, and I didn’t need to think about it. I could just take it.

The most truthful answer to the question of why I’m doing this hike is: I saw the opportunity, and I took it. I’ve been personally and professionally restless lately. The Appalachian Trail has lurked in my imagination for decades. Mica, the oldest of my three kids, is the only person I think I could hike the whole trail with, and he happened to be graduating college at the right time to start south. I happen to have the kind of job that I could just decide to take six months off from, and the kind of job I can plausibly hope to do a version of on the trail.

I can post hoc you a lot of propter hoc, and I will. But the most honest reason I’m going is that I saw the necessary pieces come into the correct alignment. It didn’t feel like making a decision, it felt like recognizing what was going to happen. The only questions I asked myself were all aimed at determining whether this recognition was correct, whether it truly was possible for Mica and me to attempt this now. I didn’t really even wonder why.

In his seminal work about one of antiquity’s greatest hikers, “ The Myth of Sisyphus ,” Camus writes of a different major life decision: “An act like this is prepared within the silence of the heart, as is a great work of art. The man himself is ignorant of it.” He’s not talking about marriage proposals or through-hiking, but important decisions are all similar. The decision to attempt this hike was prepared within the silence of my heart, during a lifetime spent in love with the outdoors. I know this isn’t a very satisfying answer, but it’s the truth, and if I can’t be completely honest, what are we even doing here?

On our last practice hike, Mica told me, “I just realized that you’re doing this instead of having a mid-life crisis.” I said that was a very generous way of expressing it, but he’s not wrong. I’m in mid-life, and I’m not in crisis. I think what I’m having is a mid-life opportunity.

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Pneumonia caused by Mycobacterium tuberculosis

a School of Life Sciences, Bengbu Medical College, Anhui, China

Yongjie Zhao

Zhuoyu qian.

b Middle School Affiliated to Guangzhou Foreign Studies University, Guangzhou, China

c Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Anhui, China

Tuberculosis (TB) is one of the top ten leading causes of death worldwide. The causative agent of TB is Mycobacterium tuberculosis . Acute tuberculous pneumonia (TP) is an acute form of pulmonary TB. However, acute TP and non-tuberculous community-acquired pneumonia can be easily confused, resulting in deterioration of TP due to delayed treatment. Therefore, rapid and accurate diagnosis of acute TP is crucial in order to stop the transmission of TB. Moreover, development of new diagnostic tools (technologies and approaches), and flexible application of different therapy schemes will help to reduce the incidence of TP and promote the goal of ending the TB epidemic.

Tuberculosis (TB) is a communicable disease caused by the bacillus Mycobacterium tuberculosis ( M. tuberculosis ). Nowadays, TB is still one of the top ten causes of death worldwide. About a quarter of the world’s population is infected with M. tuberculosis . According to WHO’s global tuberculosis report 2019, there were an estimated 10 million new TB cases in 2018, and 1.5 million people died from TB worldwide. The leading cause of death for people with HIV is TB [ 1 ].

1. Acute tuberculous pneumonia

M. tuberculosis can invade various organs of the body. Pulmonary tuberculosis (PTB) is the most common, which can mainly cause lung injury and tubercles. PTB is a typical chronic consumptive disease, but it can present as an acute pneumonia. Acute tuberculous pneumonia (TP) is similar to typical bacterial pneumonia, and it is one of the causes of childhood illness [ 2 ].

Acute TP generally refers to the clinical manifestations of community-acquired pneumonia (CAP), but the pathogen is M. tuberculosis instead of non-tuberculous bacteria or viruses [ 3 ]. TP is contagious: coughing, sneezing, laughing, and even talking can produce droplet nuclei containing M. tuberculosis . Transmission occurs when a person inhales the droplet nuclei [ 4 ].

In developing countries, M. tuberculosis is a main pathogen that cause CAP. A systematic review found that over 10% of patients with CAP in Asia were caused by M. tuberculosis [ 5 ]. HamidReza Naderi reported that 17.5% of 120 CAP patients were diagnosed with M. tuberculosis infection at Imam Reza Hospital in Mashhad, Iran [ 6 ]. Therefore, it is necessary to identify TP in patients with CAP in TB endemic areas. The global distribution of TP is consistent with that of TB ( Fig. 1 ). The incident cases mostly occur in developing countries, where many TB patients live in densely populated areas. This close contact increases the risk of cross infection.

Estimated TB incidence rates in 2018. Reproduced form global tuberculosis report 2019 ( https://www.who.int/tb/publications/global_report/en/ ). The incidence varied widely among countries in 2018.

1.1. Clinical presentation

Different from typical PTB, acute TP presents as acute respiratory infection, including dry cough, fever and chest pain. Dry cough often precedes other respiratory and systemic symptoms [ 7 ]. Duration of symptoms is often more than 2 weeks prior to admission. The clinical symptoms of acute TP are similar to those of non-tuberculous CAP. However, patients with acute TP are subjectively better than patients with non-tuberculous bacterial pneumonia with less pleural pain, toxemia and dyspnea [ 8 , 9 ]. Compare to non-tuberculous CAP, weight loss is more common in patients with acute TP. Many patients with acute TP expectorate, but hemoptysis is relatively rare [ 6 ].

Acute TP can result in severe consequences in some cases, such as acute respiratory distress syndrome (ARDS) in children [ 10 ]. Cases of acute respiratory failure caused by acute TP have also been reported [ 11 , 12 ]. Secondary diseases, including necrotizing pneumonia and destruction of the lung parenchyma, can be found in children, and were more common in HIV-infected children [ 13 ]. Jose Moreira pointed out that 59.3% of patients with TP have at least one complication; the most common ones are AIDS and diabetes [ 7 ].

1.2. Pathogenesis

Previous studies have tried to explain the pathogenesis of acute TP. M. tuberculosis propagates every 18–24 h, and it is uncommon for PTB to initially manifest as acute, rapidly progressive pneumonia. Septimus believed that this rapid progression may be an exudative hypersensitivity to aspirated tuberculoprotein, instead of the inflammatory response caused by M. tuberculosis [ 8 ]. Rich noted that the acute pneumonia could either be caused by massive M. tuberculosis infection or inhaled tuberculoprotein which cause acute exudative hypersensitivity. A study showed that in human TB, fresh pneumonia exudates were found around caseous lesions with little or no acid-fast bacilli (AFB) [ 14 ]. As early as 1931, Larson and Long injected tuberculin into the trachea of normal and TB guinea pigs respectively, confirming the hypersensitivity associated tuberculoproteins [ 15 ].

Imaging examination showed that TP was characterized by parenchymal lesions in the lung area around the affected bronchi. Bacteria and caseous substance penetrated into the periphery through these affected bronchial fistulas. TP presents a poor clinical inflammatory response that is different from the classic caseous pneumonia [ 16 ]. Clinically, dry irritating cough usually occurred a few days before fever and lung involvement, and appeared after the complete formation of fistula [ 17 ].

After the formation of TP, the outcome depends on the amount of bacteria in the caseous substance inhaled into the lungs from the lymph nodes. If there is little or no bacteria in the consolidation area, pneumonia will be relieved, which is previously called “epituberculosis” [ 18 ]. Otherwise, the disease will progress, and more necrotic cavities will spread to other areas of the lungs. Permanent lesions may occur, such as bronchostenosis. If the lesion is located in middle lobe or lingula, it will cause advanced complications such as bleeding and recurrent bacterial pneumonia [ 19 ].

1.3. TB and pneumonia

The incidence of pneumonia in PTB patients is higher than that in normal groups [ 20 ]. In some areas, such as Uganda, epidemiological analysis has shown that children with severe pneumonia have a higher incidence of PTB, accounting for 18.9% [ 21 ]. A recent study has shown that in CAP patients with streptococcus pneumoniae and M. tuberculosis coinfection, pneumococcal pneumonia is likely to provide fertile ground for reactivation of latent TB [ 22 ]. In patients with multidrug-resistant TB (MDR-TB), long-term use of medication increases the risk of secondary pneumonia. In turn, secondary pneumonia significantly delays in smear conversion to negative in patients with MDR-TB. This is also a cause to TB treatment failure [ 23 ]. Pneumonia and TB can be combined or exist one after another, and this would cause certain difficulties in identifying of the two diseases. Especially in the diagnosis of PTB, the manifestations of pneumonia are often more prominent. That may conceal the characteristics of PTB and lead to misdiagnosis.

2. Diagnosis

Patients with M. tuberculosis infection have lung damage and they may be at higher risk when pneumonia with different pathogens are raging. Once being infected with SARS-CoV-2, they are likely to develop serious COVID-19, making the treatment difficult. Therefore, timely and accurate screening of TP will help to reduce the transmission of TB.

Schwartz and Moyer proposed diagnostic criteria for TP based on its clinical manifestations: 1) Confluent dense shadows on the CXR involving at least one lobe; 2) High spiking fever; 3) Chest examination presenting signs of consolidation; and 4) Sputum examination positive for tubercle bacilli [ 24 ].

2.1. Clinical diagnosis

Imaging test: Medical imaging is an indispensable test in the diagnosis of acute TP. Morphological feature analysis of lesion is a pivotal basis for imaging diagnosis for acute TP. The radiographic characteristic of TP is homogeneous, segmental consolidation on CXR, which is interpreted by chest radiologists as bacterial pneumonia [ 25 ]. A retrospective study on 59 TP patients found that pulmonary consolidation of most cases (67.8%) appeared in upper lobes, with the right lobe predominate. 9 cases’ pulmonary consolidation were found in the middle lobe [ 7 ].

If a chest computed tomography (CT) scan is performed, the result will also be homogeneous consolidation [ 26 ]. Positron emission tomography combined with CT (PET/CT), which measures pulmonary inflammation through cellular uptake of 18 F-labelled fluorodeoxyglucose, was very sensitive to detect M. tuberculosis early infection [ 27 ].

Serologic test: Leukocytosis was observed in only 35.6% of the TP patients [ 7 ]. The white blood cell count rarely exceeds 15,000/cu mm [ 8 , 9 ]. Some potential biomarkers in serum have been discovered in the diagnosis of TP. Researchers have constructed TB prediction model by detecting the levels of three iron biomarkers in serum (including serum iron, ferritin and transferrin) that can diagnose TB well. It can distinguish PTB from non-TB pneumonia. And it is hopeful to expand the diagnostic method of TP [ 28 ].

Microbiological tests: The AFB smear microscopy of the sputum or the bronchial washing specimens from TP patient is an effective and reliable method. Sputum smear microscopy is still the main laboratory test in many resource-limited settings [ 29 ]. The respiratory specimen of TP patient usually contains fewer bacteria and may require multiple samples for AFB test. The quality of microscopy diagnosis is often not guaranteed, as this test was noted to have poor sensitivity (between 30% and 70%) [ 30 ]. A retrospective observational study showed that 27 of 70 PTB patients (38.5%) were AFB smear-negative. These patients were more likely to be treated as non-tuberculous pneumonia and be admitted to the general ward without quarantined during hospitalization [ 31 ].

Using an automated screening system can improve the utility of this older diagnostic test-smear microscopy. Law has developed a computer-aided whole smear screening system, that can be used to detect AFB from respiratory specimens under general optical microscopy or fluorescence microscopy. So the staff workload can be reduced [ 32 ].

2.2. Differential diagnosis

Although there are many diagnostic methods, one of the challenges in the diagnosis of TP is to distinguish it from non-tuberculous CAP. In some areas with high TB prevalence, it is easy to misdiagnose PTB as CAP (such as community-acquired Tsukamurella pneumonia) due to similar symptoms [ 33 ]. Nonetheless, the two still have their own characteristics ( Table 1 ). In the course of CAP treatment, acute TP should be considered when the patient experiences ineffective antibiotic treatment. And the patient should be screened for HIV infection [ 34 ].

Table 1

Difference between tuberculous pneumonia and non-tuberculous CAP.

Two inflammatory biomarkers, C-reactive protein (CRP) and procalcitonin (PCT), have shown the important clinical significance in identifying TB, Pneumocystis jirovecii pneumonia, and bacterial pneumonia in HIV patients [ 35 ]. PCT levels in patients with PTB were significantly lower than those non-tuberculous CAP patients [ 6 ]. PCT tests have acceptable sensitivity and specificity in distinguishing TB from bacterial pneumonia [ 36 ]. However, a prospective cohort study showed that using CRP and PCT to identify TB from CAP patients has limited value [ 35 ]. Moreover, CRP has high sensitivity but low specificity in diagnosis of HIV-associated TB [ 37 ]. Accordingly, CRP and PCT can be used as reference indicators for the diagnosis of TP. In addition, Japanese researchers distinguished TP from non-tuberculous pneumonia by testing serum IFN-γ, matrix metalloproteinases-1 and-9 (MMP-1 and MMP-9), and periostin [ 38 ].

The serum neutrophil-lymphocyte count ratio (NLR) levels of PTB patients were significantly lower than patients with bacterial CAP [ 39 ]. NLR can be used to distinguish PTB from bacterial CAP in the initial diagnosis. Besides, a study pointed out that the values of delta neutrophil index (DNI) of PTB patients were lower than those of CAP patients. Initially elevated DNI may help to rule out the possibility of PTB and also serve as an important potential diagnostic indicator to clinically distinguish between PTB patients and CAP patients [ 40 ].

A CT-based predictive nomogram built with pulmonary consolidation region, lymph node region and a clinical factor (duration of fever) can distinguish childhood PTB from CAP conveniently [ 26 ].

2.3. Etiologic diagnosis

Mycobacterial culture: M. tuberculosis culture, which is regarded as the “gold standard” for TB diagnosis by WHO, provides accurate and reliable results for acute TP diagnosis. Culture-positive strains can be used for subsequent strain identification and drug sensitivity testing. But traditional solid and liquid media culture have several limitations, including poor practicability, bacterial cross-contamination, and long culture time (about 2 months). Automated or semi-automated liquid culture system can significantly decrease the growth time of M. tuberculosis and shorten the diagnosis time of drug-sensitive M. tuberculosis . However, this system also takes about 14 days to detect M. tuberculosis [ 41 ], which is disadvantageous to the rapid diagnosis for TP.

Immunological diagnosis: IFN-γ release assays (IGRAs) are originally developed to diagnose latent TB, and are widely used to detect M. tuberculosis infection with high specificity and sensitivity [ 42 ]. But the high cost limits their application in developing countries. Moreover, some studies have shown that severe diabetes may affect the results of IGRAs [ 43 ]. The TS-SPOT assay, which is also based on IFN-γ detection, has the characteristics of low cost-effectiveness and high sensitivity. So it is a useful auxiliary method for rapid diagnosis of M. tuberculosis infection in low-income and high-incidence environment [ 44 ]. IGRA-ELISA can be used for large-scale detection, so it is easy to operate and can save manpower. In addition, there is a good correlation and consistency between IGRA-ELISA and T-SPOT.TB in the diagnosis of TB [ 45 , 46 ].

Molecular assays: The Center for Disease Control and Prevention (CDC) recommends that in addition to smear microscopy, at least one nucleic acid amplification (NAA) test, including polymerase chain reaction (PCR), should be performed for every suspected PTB patient [ 47 , 48 ]. A rapid, automated NAA test-Xpert MTB/RIF assay, is the only approach recommended by WHO for rapid diagnosis of TB and rifampicin resistance [ 49 ]. But this technology is not affordable in high-TB burden countries with limited resources [ 50 ]. And children are less sensitive than adults [ 49 ]. Xpert MTB/RIF Ultra assay is more sensitive than Xpert MTB/RIF assay in detecting TB patients complicated with paucibacillary disease or HIV, and is more sensitive to specimens with low bacillus content [ 51 ]. Therefore it can overcome the limitation of Xpert MTB/RIF assay. The detection of bacterial RNA can target viable M. tuberculosis . Bacterial load in sputum can be quantified through detecting 16S ribosomal RNA [ 52 ], as sensitive as solid culture [ 53 ].

In contrast to M. tuberculosis culture, one of the main advantages of molecular test is the rapid diagnosis that the results can be obtained on the same day [ 54 ]. However, the premise of rapid PCR-based test is to obtain a respiratory specimen, which is not practical for sputum samples of inadequate quality or patients who cannot spit. In order to collect specimens more effectively, Williams CM and his colleagues developed face-mask sampling, a highly efficient and non-invasive method for detecting exhaled M. tuberculosis output. This approach can detect early infection [ 55 ].

3. Treatment

3.1. anti-tb therapy.

There are two types of anti-tuberculosis drugs in clinical use currently: first-line and second-line antibiotics. First-line drugs include rifampicin, streptomycin, isoniazid, etc. Second-line drugs include kanamycin, ciprofloxacin, ethionamide, etc. [ 56 ]. TB treatment requires a combination of multiple antibiotics with a treatment cycle of 6–9 months or even 2 years. However, the combination of multiple antibiotics, non-standard medication and insufficient medication duration are likely to produce strains of drug resistance [ 57 ]. These strains are defined as MDR. The main drugs used to treat MDR-TB are fluoroquinolones (FQ) and lastline injections (amikacin, kanamycin and capreomycin). Their use may lead to the emergence of extensively drug-resistant (XDR) strains that developed additional resistance mechanisms to FQ and aminoglycosides [ 58 ]. Therefore, the use of FQ as an empirical treatment for CAP in TB endemic areas should implement short-course (5–10 days) regimen to reduce the appearance of FQ-resistant M. tuberculosis [ 59 ]. This emphasizes the importance of rapid screening for M. tuberculosis infection in CAP patients [ 60 ]. It has been reported that delamanid and bedaquiline can be used in combination to treat XDR-TB and MDR-TB. Increasing evidence shows that this medicine combination is likely to be acceptable [ 61 , 62 ].

A series of candidate host-directed and immune-based therapies can accelerate the eradication of M. tuberculosis . They are being developed and will be used as adjuvant therapies to shorten the course of treatment, prevent permanent lung injury and improve the outcome of MDR-TB treatment [ 63 ]. It has been reported that a female with TP complicated with severe ARDS and disseminated intravascular coagulation has been successfully treated by high frequency oscillatory ventilation, vasopressor support, anti-TB therapy, intravenous immunoglobulin and recombinant soluble human thrombomodulin [ 10 ].

Inhaled drug therapy for TB can be used to supplement traditional oral drug therapy. The advantage of inhalation therapy for TB is that it can deliver high concentrations of drugs to the lungs, which is the main sites of M. tuberculosis infection. Inhalation therapy for TB is a potentially strategy that needs to be evaluated in clinical studies [ 64 ]. There is a precedent for inhalation of beclomethasone dipropionate in acute TP patients complicated with asthma [ 65 ]. A recent article described the effect of intrapulmonary administration on local and systemic pharmacokinetics and showed how inhaled administration achieved high levels in the lung along with low levels of systemic absorption, which will help avoid toxicity [ 66 ]. Therefore, as one of the alternative strategies for traditional medicine, inhalation therapy is a potential method for the treatment of TP.

3.2. Anti-inflammatory therapy

After M. tuberculosis is engulfed by alveolar macrophages, the infected macrophages will release pro-inflammatory cytokines [ 67 ]. Increasing evidence supports that inhibiting excessive and harmful inflammatory responses may reduce mycobacterial dissemination without inducing immunopathology [ [68] , [69] , [70] ]. Therefore, anti-inflammatory drugs should be considered in treatment for TP except antibiotics that target M. tuberculosis . A study found that PTB patients with acute renal failure who received corticosteroids had lower mortality than patients without corticosteroids [ 71 ]. It may be related to the anti-inflammatory properties of glucocorticoids and receptor agonists, such as dexamethasone and prednisone [ 72 ]. Corticosteroids can prevent immune reconstitution inflammatory syndrome in TB/HIV co-infection by improving TB lung pathology [ 73 ]. Survival benefits for TB meningitis have been proved [ 74 ]. Another study reported that M. tuberculosis associated necrotizing pneumonia was successfully treated by the initiation of corticosteroid followed by anti-TB drugs [ 75 ]. Andy Ruiz et al. found that Resolvin D1 and Maresin 1 can induce anti-inflammatory mechanism of human macrophages and produce different antimicrobial effectors to control intracellular growth of M. tuberculosis [ 76 ]. Their clinical application in patients with TP needs to be addressed in the future.

3.3. Pulmonary function repair

Although the cure rate of new cases of TB has reached 85% in 2017, the chronic lung injury after PTB should not be ignored. Compared with the entire population, the morbidity and mortality of TB survivors were higher [ 77 , 78 ]. Pulmonary consolidation caused by TP can cause destructive damage to lung tissue, which is typically marked by pulmonary cavity [ 79 , 80 ]. Therefore, chronic lung damage after treatment of M. tuberculosis infection should be considered [ 78 , 81 ], and lung function repair should be performed to prevent M. tuberculosis reinfection.

Studies have found that inhibiting matrix metalloproteinase may reduce lung damage in people with history of tuberculosis, but it still needs to be proved by clinical trials [ 82 ]. Some traditional Chinese medicines may have repairing and protecting effects on TB-induced lung damage. Sinomenine, which was originally extracted from a Chinese herbal medicine- Sinomenium acutum , can attenuate acute lung injury by inhibiting inflammation and reducing oxidative stress [ 83 ]. Radix Astragali, a traditional Chinese medicine, can protect cells and tissues from oxidative stress by scavenging free radicals and reactive oxygen species, and finally providing significant protection against lung injury [ 84 ].

Climate change, air pollution and air allergens, etc. can affect cardiopulmonary health [ 85 ]. In the elderly, the increase in temperature and relative humidity are related to the decline in lung function [ 86 ]. Therefore, elderly patients with TP should pay attention to living in a suitable environment after recovery. Pablo A Salcedo et al. used meta-analysis to quantify the effect of exercise training on indices of pulmonary function in adults with chronic lung disease, and pointed out that whole body exercise training can effectively improve lung function, especially the vital capacity index [ 87 ]. Exercise can also improve the lung function of children with cystic fibrosis [ 88 ]. Therefore, proper exercise is indispensable after TP treatment.

3.4. Vaccine prevention and treatment

Vaccine is the best way to prevent TP. Bacille Calmette-Guérin (BCG) is the only licensed vaccine against M. tuberculosis infection [ 89 ]. Although BCG can effectively protect infants and young children from M. tuberculosis infection, its efficacy on PTB varies, especially among adults [ 90 ]. Therefore, the emergence of new vaccines or new usage of existing vaccine is still worth looking forward to. The discovery of intravenous BCG by Darrah and colleagues provided greater protection to prevent TB [ 91 ]. Juan I. Moliva et al. pointed out that petroleum can be used to selectively remove many inflammatory lipids (including trehalose dimycolate, trehalose dimycolate, mycoside B, triacylglycerols, and phthiocerol dimycocerosates) of BCG, without affecting the vitality of BCG. This would make the processed vaccine safer by reducing inflammation [ 92 ].

In addition, there are many candidate vaccines under development. For example, a modified vaccine-MVA85A, which can express Ag85A, is the first therapeutic vaccine that undergo clinical efficacy trials in more than 60 years. However, the infants who received MVA85A as booster vaccination after BCG have been found no significant improvement in TB protection during three years’ follow-up [ 93 ]. Thomas H. King et al. found that a new Saccharomyces cerevisiae immunotherapeutic vaccine named GI-19007 had immunogenicity in mice. This fusion vaccine can elicit strong IFN-γ and IL-17 responses. The survival rate of guinea pigs treated with GI-19007 and BCG was higher than BCG alone, so it may be used to limit lung injury and expand chemotherapy regimens for TB treat [ 94 ]. With the rapid development of immunology and molecular biology, others new TB vaccines have emerged to provide new hope for the prevention and treatment of TB, including inactivated vaccines, recombinant live vaccines, attenuated live vaccines, subunit vaccines, and DNA vaccines, etc. [ 95 ].

4. Concluding remarks

Lung infection with M. tuberculosis usually presents as a chronic consumptive disease, but it can also cause acute pneumonia. Under the cover of various types of pneumonia, TP can be easily misdiagnosed, leading to more serious disease progression. No matter in the areas with high or low prevalence of TB, the attending doctor should be alert to M. tuberculosis infection for patients with doubtful pneumonia.

High sensitivity, high specificity and easy-to-use diagnostic tests are necessary for the rapid and accurate detection of M. tuberculosis infection. However, it’s worth noting that many diagnostic tests are inadequate for young children who are prone to TP. In low income areas where TB is prevalent, affordability of diagnostic tools is also an important issue.

One difficulty in TP treatment is drug-resistant TB. Drug screening of infected patients will undoubtedly increase the treatment effect. TP is more common in special populations, such as children, the elderly, and HIV patients, individualized treatment should also be considered. Of course, the clinical application of new vaccines with stronger protection is more worthy of expectation, so as to realize the long-cherished desire to completely eliminate TB.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements

The work & review were supported by the Research Foundation of Anhui Provincial Education Department (KJ2019A0317 and KJ2019A0361), the Natural Science Research Foundation of Anhui Provincial (1708085MH192), the Research Fund of Bengbu Medical College (BYKY1811ZD, BYKY1835ZD and BYKY2019020ZD), the National Training Programs of Innovation and Entrepreneurship for Undergraduates (201810367037, 201910367007 and 201810367007).